gebhart/patrepeval huggingface dataset:
Keynote: The Effects of Microgrooved Structures on Cell shape and Actomyosin Organization (2016)

The stra tegies to regulate cell migration, growth, and differentiation are fundamental for tissue engineering. It has been shown that cell shape and intracellular actomyosin organization regulate these cellular processes. The cell shape and actin cytoskeletal organization are affected by various cues in the tissue microenvironment [1]. Our aim here is to provide a basis for an external control of these cellular processes by clarifying the effect of extracellular microgrooved structures on cell shape and actin cytoskeletal tension. We fabricated a polydimethylsiloxane (PDMS) cell culture substrate consisting of microstructured surfaces with of a major groove and branched grooves in order to control cell shape and actomyosin organization externally. The major groove was designed to guide cell body penetration, and the branched grooves were designed to guide cellular protrusion into them. Swiss3T3 fibroblasts were cultured on the substrate for 24 hours. Then, the cells were fixed and processed to visualize actin filaments and phosphorylated myosin. On the microstructured substrate, about a half of the cells penetrated into the grooved structure as predicted. On the other hand, the other cells were grown on the grooves. In both of the two groups, the cells show various shapes. In the penetrated groups, disappearance of the stress fibers was observed. This observation indicated that the major groove had an effect to suppress actin stress fiber formation in the cell body by the downregulation of Rho. Furthermore, these cells had a tendency to form thin actin protrusions into the branched grooves. These actin protrusions contained no phosphorylated myosin, thus they were assumed to be filopodia, which indicated the upregulation of cdc42. This result of actin filaments and phosphorylated myosin distribution in the cells in the microgrooved structure suggests that the microgrooves can be utilized for external control of local activities of Rho and cdc42. These small GTPases are known to be regulators of various cellular processes, involving cell migration, growth, and differentiation [2, 3]. Thus, our findings would be a basis for designing microstructures on cell and tissue culture substrate for tissue engineering. Keywords: Microgroove, Fibroblast, Actin Cytoskeleton, Myosin Phosphorylation References [1] Miyoshi, H. and T. Adachi (2014) Topography Design Concept of a Tissue Engineering Scaffold for Controlling Cell Function and Fate Through Actin Cytoskeletal Modulation, Tissue Engineering Part B-Reviews. 20, 609-627. [2] McBeath, R., D.M. Pirone, C.M. Nelson, K. Bhadriraju, and C.S. Chen (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment, Dev Cell. 6, 483-95. [3] Raftopoulou, M. and A. Hall (2004) Cell migration: Rho GTPases lead the way, Developmental Biology. 265, 23-32.
Hantzsch Dihydropyridine: An Effective and Convenient Regioselective Reducing Agent for 5‐Benzylidene‐2,4‐thiazolidinedione Derivatives. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Poly(Vinyl Alcohol) Fiber Reinforced High Density Poly(Ethylene) Composites: Melting and Crystallization Behavior (2018)

In the present study, high density poly(ethylene) (HDPE)/poly(vinyl alcohol) (PVA) fiber composites were prepared via melt blending technique using a co-rotating twin screw extruder (TSE). The effect of four different PVA fiber concentrations (i.e. 0, 5, 10, 20 wt%) on the melt and crystallization behavior of the HDPE/PVA fiber composites were investigated. The surface morphology of the composites was analyzed by a scanning electron microscopy (SEM). Whereas, the melt and crystallization behavior of the composites were analyzed by a differential scanning calorimetry (DSC). The SEM analysis on the cryo-fractured surface of the HDPE/PVA fiber composites exhibited that the PVA fibers were well blended/distributed in the HDPE matrix. Additionally, the DSC test results showed that the addition of PVA fiber in the HDPE matrix did not significantly change the melting peak temperature (T m ) of the composites. Furthermore, a slight decrease of the crystallization peak temperature (T c ) can be observed when the PVA fiber was incorporated in the HDPE matrix, which indicated a weak nucleation ability of the PVA fibers in the HDPE crystallization process. The same trend was also observed for the crystallinity index (X c ). The crystallinity index of the composites decreased with increasing PVA fiber loadings.
Addition of amino acid moieties to lapatinib increases the anti‐cancer effect via amino acid transporters (2013)

Anti-cancer agents delivered to cancer cells often show multi-drug resistance (MDR) due to expulsion of the agents. One way to address this problem is to increase the accumulation of anti-cancer agents in cells via amino acid transporters. Thus, val-lapatinib and tyr-lapatinib were newly synthesized by adding valine and tyrosine moieties, respectively, to the parent anti-cancer agent lapatinib without stability issues in rat plasma. Val-lapatinib and tyr-lapatinib showed enhanced anti-cancer effects versus the parent lapatinib in various cancer cell lines, including human breast cancer cells (MDA-MB-231, MCF7) and lung cancer cells (A549), but not in non-cancerous MDCK-II cells. A glutamine uptake study revealed that both val-lapatinib and tyr-lapatinib, but not the parent lapatinib, inhibited glutamine transport in MDA-MB-231 and MCF7 cells, suggesting the involvement of amino acid transporters. In conclusion, val-lapatinib and tyr-lapatinib have enhanced anti-cancer effects, likely due to an increased uptake of the agents into cancer cells via amino acid transporters. The present data suggest that amino acid transporters may be an effective drug delivery target to increase the uptake of anti-cancer agents, leading to one method of overcoming MDR in cancer cells.
Pulse Oximeter Plethysmographic Waveform Changes in Awake, Spontaneously Breathing, Hypovolemic Volunteers (2011)

McGrath, Susan P.*; Ryan, Kathy L.†; Wendelken, Suzanne M.*; Rickards, Caroline A.†; Convertino, Victor A.† Author Information
The Effect of Conservative Treatment for the Calcific Tendinitis on Gluteus Medius Tendon (2011)

Calcific tendinitis on gluteus medius tendon of the amateur athletes were reviewed, and a study on the therapeutic effect of conservative treatment methods. From January 2003 to December 2010, among the patients who had been treated with calcific tendinitis on gluteus medius tendon, there were nine patients available to monitor more than a year as outpatients. ten cases were observed from them and were retrospectively analyzed and magnetic resonance examinations were performed in every case. All of the ten cases were initially treated with non-steroid anti-inflammatory oral doses. If a non-steroid anti-inflammatory treatment could not relieve pain or caused an aggravation of a condition, a local steroid injection was enforced. There were responses to non-steroid antiinflammatory oral doses of therapeutic methods in four cases and the time required for the symptoms to be improved was approximately 3 weeks (range: 1-3 weeks). In the remainder of six cases, conditions got worsened or did not improve even after 3 weeks. In these cases, the condition was altered for better in 3 days (range: 1-3 days) by using local steroid injections. There was no recurrence in all cases. The amateur athlete with a severe pain around his or her hip joint should be questioned with calcific tendinitis on gluteus medius tendon and differential diagnosis of hip around diseases. After calcific tendinitis was diagnosed, initial treatment was considered conserevative treatment. Although it is invasive, the initial treatment with a local steroid injection is considered to be helpful in treating amateur athletes with calcific tendinitis.
Experimental and Numerical Investigation of Environmental Barrier Coated Ceramic Matrix Composite Turbine Airfoil Erosion (2018)

Ceramic matrix composite (CMC) have higher temperature durability and lower density property compared to nickel-based super-alloys which so far have been widely applied to hot section components of aero-engines/gas turbines. One of promising CMC systems, SiC–SiC CMC is able to sustain its mechanical property at higher temperature, though it inherently needs environmental barrier coating (EBC) to avoid oxidation. There are several requirements for EBC. One of such critical requirements is its resistance to particle erosion, whereas this subject has not been well investigated in the past. The present work presents the results of a combined experimental and numerical research to evaluate the erosion characteristics of CMC + EBC material developed by IHI. First, experiments were carried out in an erosion test facility using 50 μm diameter silica as erosion media under typical engine conditions with velocity of 225 m/s, temperature of 1311 K, and impingement angles of 30, 60, and 80 deg. The data displayed brittle erosion mode in that the erosion rate increased with impact angles. Also, it was verified that a typical erosion model, Neilson–Gilchrist model, can reproduce the experimental behavior fairly well if its model constants were properly determined. The numerical method solving particle-laden flow was then applied with the tuned erosion model to compute three dimensional flow field, particle trajectories, and erosion profile around a generic turbine airfoil to assess the erosion characteristics of the proposed CMC + EBC material when applied to airfoil. The trajectories indicated that the particles primarily impacted the airfoil leading edge and the pressure surface. Surface erosion patterns were predicted based on the calculated trajectories and the experimentally based erosion characteristics.
<i>para</i> ‐substituted methcathinones as selective and unselective inhibitors of human dopamine and serotonin transporters (2019)

Methcathinone (MCAT) is a compound belonging to the class of cathinones which targets monoamine transporters including DAT and SERT. Despite the importance of DAT and SERT as drug targets in several neurological disorders, the key factors underlying the selectivity profiles of their inhibitors are still poorly understood. Recent findings from rat synaptosomes suggested that increasing the volume of the para‐substituent of MCAT results in a swap of the selectivity between human DAT and SERT (1). Docking studies hint towards Ser149 in DAT and Ala169 in SERT as key residues involved in the difference of activity between DAT and SERT (2). The aims of the present biochemical and pharmacological study are to understand (i) which chemical properties (e.g. volume, polarity, or lipophilicity) of the para‐substituent influence the selectivity profile of MCAT between DAT and SERT, and (ii) whether Ser149 in DAT and Ala169 in SERT can be experimentally verified as key residues. Hence, we combined in silico ‐driven synthesis, mutagenesis, and radio‐tracer flux assays in HEK293 cells expressing the human DAT and SERT wild‐type and respective mutants. We found that only MCAT and the para‐CF 3 ‐MCAT showed high selectivity, 200‐fold for DAT/SERT ‐ and 25‐fold for SERT/DAT, respectively. This suggests that the high selectivity achieved is determined rather by specific features of these compounds than by the volume of the para‐substituent. Accordingly, we were not able to find any correlation between the selectivity profile of the tested 4MCATs with either volume, polarity, or lipophilicity parameters. Next, based on our results, we tested the hypothesis that the two amino acids in SERT and DAT do not suffice to explain the selectivity between SERT and DAT. We have tested the para‐substituted methcathinones in the swapping mutations DAT Ser149Ala and SERT Ala169Ser and in line with our hypothesis, these mutations did not revert the selectivity profile found in the wild‐type transporters. Our findings rather suggest that the SERT selectivity achieved by the introduction of the CF 3 ‐group in the para‐position of MCAT is not dependent on the volume of the para‐substituent but on specific chemical features of the fluorine atoms which may influence the on and off rate of the MCAT molecule on DAT and SERT. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Supplementary Figures 1-4 from Triple Gene-Deleted Oncolytic Herpes Simplex Virus Vector Double-Armed with Interleukin 18 and Soluble B7-1 Constructed by Bacterial Artificial Chromosome–Mediated System (2023)

Supplementary Figures 1-4 from Triple Gene-Deleted Oncolytic Herpes Simplex Virus Vector Double-Armed with Interleukin 18 and Soluble B7-1 Constructed by Bacterial Artificial Chromosome–Mediated System
Replicated mask surface roughness effects on EUV lithographic patterning and line edge roughness (2011)

To quantify the roughness contributions to speckle, a programmed roughness substrate was fabricated with a number of areas having different roughness magnitudes. The substrate was then multilayer coated. Atomic force microscopy (AFM) surface maps were collected before and after multilayer deposition. At-wavelength reflectance and total integrated scattering measurements were also completed. Angle resolved scattering based power spectral densities are directly compared to the AFM based power spectra. We show that AFM overpredicts the roughness in the picometer measurements range. The mask was then imaged at-wavelength for the direct characterization of the aerial image speckle using the SEMATECH Berkeley Actinic Inspection Tool (AIT). Modeling was used to test the effectiveness of the different metrologies in predicting the measured aerial-image speckle. AIT measured contrast values are 25% or more than the calculated image contrast values obtained using the measured rms roughness input. The extent to which the various metrologies can be utilized for specifying tolerable roughness limits on EUV masks is still to be determined. Further modeling and measurements are being planned.
Synchronization and NRZ-to-RZ conversion of 10 Gbit/s Ethernet-like data packets and subsequent optical TDM multiplexing to 330 Gbit/s (2011)

A time lens system synchronizes a 10G Ethernet asynchronous data frame to a local master clock and converts the NRZ-frame to an RZ-frame and multiplexes it into a 330 Gbit/s aggregated Optical TDM signal.
Further Studies on Nociceptin-Related Peptides:  Discovery of a New Chemical Template with Antagonist Activity on the Nociceptin Receptor (2000)

Three series of nociceptin (NC)-related peptides were synthesized and their abilities (i) to bind to the NC sites expressed in mouse forebrain membranes, (ii) to inhibit the electrically evoked contraction of the mouse vas deferens, and (iii) to inhibit forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells expressing the human recombinant NC receptor (CHONCR) were investigated. The compounds of the first series (a series) have an ordinary Xaa1-Gly2 bond, those of the second series (b series) have a Xaa1psi(CH2-NH)Gly2 pseudopeptide bond, and those of the third series (c series) have a peptoid (Nxaa1-Gly2) structure. The affinity values measured in the binding assay and in the two functional assays with the compounds of the three series showed high levels of correlation. Thus, (I) the compounds of the a series in which Phe1 was substituted with Tyr, Cha, or Leu acted as potent NC receptor agonists; (II) the b series compounds behaved as NC receptor antagonists in the mouse vas deferens and as full agonists in CHO(NCR) cells with different potencies depending on the first amino acid residue, [Phe1psi(CH2-NH)Gly2]NC(1-17)NH2 and [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 being the most potent compounds; (III) the compounds of the third series were all inactive both as agonists and as antagonists with the exception of [Nphe1]NC(1-17)NH2 and [Nphe1]NC(1-13)NH2, which behaved as NC receptor antagonists both in the isolated tissue and in CHO(NCR) cells (pKB 6.1-6.4). In conclusion, this study demonstrates that chemical requirements for NC receptor agonists are different from those of antagonists. Moreover, modifications of the steric orientation of the aromatic residue Phe1 in the NC sequence as obtained with the pseudopeptide bond between Phe1 and Gly2 or with the displacement of the benzyl side chain by one atom, as in Nphe1, lead respectively to reduction or elimination of efficacy. Indeed, in contrast to [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 which has been reported to exhibit agonist activity in several assays involving either central or recombinant NC receptors, [Nphe1]NC(1-13)NH2 antagonizes the effect of NC at human recombinant NC receptors and in the mouse tail withdrawal assay.
AKT Inhibition Modulates H3K4 Demethylase Levels in PTEN-Null Prostate Cancer (2018)

Hyperactivated AKT kinase due to loss of its negative regulator PTEN influences many aspects of cancer biology, including chromatin. AKT primarily regulates acetyl-CoA production and phosphorylates many histone-modulating enzymes, resulting in their activation or inhibition. Therefore, understanding the therapeutic impact of AKT inhibition on chromatin-related events is essential. Here, we report that AKT inhibition in prostate-specific PTEN knockout mice significantly induces di- and trimethylation of H3K4 with concomitant reduction in H3K9 acetylation. Mechanistically, we observed that AKT inhibition reduces expression of the H3K4 methylation-specific histone demethylases KDM5 family, especially KDM5B expression at transcriptional levels. Furthermore, we observed that AKT negatively regulates miR-137 levels, which transcriptionally represses KDM5B expression. Overexpression of miR-137 significantly reduced KDM5B and increased H3K4 methylation levels but failed to change AKT phosphorylation. Overall, we observed that AKT transcriptionally regulates KDM5B mainly via repression of miR-137. Our data identify a mechanism by which AKT kinase modulates the prostate cancer epigenome through regulating H3K4 methylation. Additional studies on AKT inhibition-mediated induction of H3K4 methylation will help in designing strategies to enhance the therapeutic efficacy of PI3K/AKT inhibitors.
Short single-wedge stems have higher risk of periprosthetic fracture than other cementless stem designs in Dorr type A femurs: a finite element analysis (2020)

Our results suggest the risk of intraoperative and postoperative periprosthetic fracture with THA in a Dorr A femur is highest with short single-wedge stems and lowest with standard-length single-wedge stems. Consideration may be given to minimising the use of short single-wedge stems in THA. Implant-specific sites of highest strain should be carefully inspected for fracture.
Why are the Batteries in the Microwave?: Use of Semantic Information Under Uncertainty in a Search Task (2016)

Observers use prior expectations to inform their searching behavior within an environment to facilitate efficient visual search (Aydemir et al., 2013). Search decisions may reflect this bias even when it is contradicted by recent experience (Võ & Wolfe, 2012; 2013). We asked whether searchers can learn to incorporate evidence that contradicts their prior expectations with practice. To estimate prior expectations, 185 participants rated how likely common household objects were to be found in each of 12 locations (6 in the living room and 6 in the kitchen). Then, a separate group of 10 participants searched through two virtual rooms (kitchen and living room) for one of 3 target objects. Objects were hidden from view in the scene and revealed by a mouseclick. Points were awarded for finding a target before the end of each 30s trial, and more points were awarded for searching quickly. Time was expended in clicking locations and traveling between rooms. Three search environments were created in which targets appeared in likely, unlikely, or uniform locations, where location likelihood was determined from the initial ratings. The three environments were tested in separate blocks of trials. We found that there were two types of searchers: those who adapted to the environment quickly when the episodic information did not match prior expectations, and those who required repeated searches in order to learn new sets of expectations. Results were consistent with a Bayesian decision model in which the prior expectations were either consistent with the ratings, inverted, or uniform. Searchers who took more time to adapt to the environment either did not construct a new prior to account for recent experience, or assumed all target locations were random. The findings indicate different individual preferences to form new expectations to fit recent experiences. Meeting abstract presented at VSS 2016
Clinical and Serologic Manifestations of Autoimmune Disease in MRL-<i>lpr/lpr</i> Mice Lacking Nitric Oxide Synthase Type 2 (1997)

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl-arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL-lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL-lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL-lpr/lpr mice to the N4 generation. MRL-lpr/lpr littermates homozygous for disrupted NOS2 (-/-), heterozygous for disrupted NOS2 (+/-), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (-/-) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/-) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (-/-) animals, whereas that of (+/+) was high and (+/-) intermediate. The (-/-) mice developed glomerular and synovial pathology similar to that of the (+/-) and (+/+) mice. However, (-/-) mice and (+/-) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (-/-) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.