gebhart/patrepeval huggingface dataset:
Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains (2018)

Bromodomains have been pursued intensively over the past several years as emerging targets for the development of anticancer and anti-inflammatory agents. It has recently been shown that some kinase inhibitors are able to potently inhibit the bromodomains of BRD4. The clinical activities of PLK inhibitor BI-2536 and JAK2-FLT3 inhibitor TG101348 have been attributed to this unexpected polypharmacology, indicating that dual-kinase/bromodomain activity may be advantageous in a therapeutic context. However, for target validation and biological investigation, a more selective target profile is desired. Here, we report that benzo[e]pyrimido-[5,4- b]diazepine-6(11H)-ones, versatile ATP-site directed kinase pharmacophores utilized in the development of inhibitors of multiple kinases, including several previously reported kinase chemical probes, are also capable of exhibiting potent BRD4-dependent pharmacology. Using a dual kinase-bromodomain inhibitor of the kinase domains of ERK5 and LRRK2, and the bromodomain of BRD4 as a case study, we define the structure-activity relationships required to achieve dual kinase/BRD4 activity, as well as how to direct selectivity toward inhibition of either ERK5 or BRD4. This effort resulted in identification of one of the first reported kinase-selective chemical probes for ERK5 (JWG-071), a BET selective inhibitor with 1 μM BRD4 IC<sub>50</sub> (JWG-115), and additional inhibitors with rationally designed polypharmacology (JWG-047, JWG-069). Co-crystallography of seven representative inhibitors with the first bromodomain of BRD4 demonstrate that distinct atropisomeric conformers recognize the kinase ATP-site and the BRD4 acetyl lysine binding site, conformational preferences supported by rigid docking studies.
Standard negation: the curious case of South America (2022)

Abstract This study compares standard negation in the indigenous languages of South America to the rest of the world. We show that South American languages not only prefer postverbal negation to preverbal negation and negative morphology to syntax, but postverbal morphological negation to any other negation strategy. The predominance of this strategy makes South America distinct from other macro-areas. The study also considers the areal distribution of negation on the South American continent. It shows that negation strategies each have their own concentration area. Postverbal morphological negation, which is the dominant strategy, turns out to be concentrated in the northwest of the continent, with the highest density around the boundaries between Colombia, Peru and Brazil. We suggest that the preference for postverbal morphological negation in South America is likely to be the result of language-internal mechanisms of negation renewal, coupled with language contact.
1A2-E06 Dynamics of Passive Operation and Haptic Perception Phenomena (2007)

Though the perceived shift quality for a manual transmission is very important, a useful design framework of the operation feeling has never established. For the sake of simplicity and clarity as possible, we develop the shift operation system with a lock-ball mechanism. The dynamics of shift operation, which results from the interaction between human's arm and the shifter, is discussed. And, the shift operation simulator including a stretch reflex model is developed. Furthermore, we propose a unique approach that is the basic study including neuroscience for the haptic perception phenomena which are concerned with the shift feeling.
Synthetic preparation and immunological evaluation of β-mannosylceramide and related N-acyl analogues (2020)

The synthesis of the invariant natural killer (iNK) T cell agonist β-mannosylceramide along with a series of fatty amide analogues is reported. Of the six β-glycosylation protocols investigated, the sulfoxide methodology developed by Crich and co-workers proved to be the most effective where the reaction of a mannosyl sulfoxide and phytosphingosine derivative gave a key glycolipid intermediate as a 95 : 5 mixture of β- to α-anomers in high yield. A series of mannosyl ceramides were evaluated for their ability to activate D32.D3 NKT cells and induce antitumour activity.
YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity (2019)

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates glucose, lipid, and energy homeostasis. While gene expression of FGF21 is regulated by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha in the fasted state, little is known about the regulation of trafficking and secretion of FGF21. We show that mice with a mutation in the Yip1 domain family, member 6 gene (<i>Klein</i>-<i>Zschocher</i> [<i>KLZ</i>]; <i>Yipf6</i><sup><i>KLZ/Y</i></sup> ) on a high-fat diet (HFD) have higher plasma levels of FGF21 than mice that do not carry this mutation (controls) and hepatocytes from <i>Yipf6</i><sup><i>KLZ/Y</i></sup> mice secrete more FGF21 than hepatocytes from wild-type mice. Consequently, <i>Yipf6</i><sup><i>KLZ/Y</i></sup> mice are resistant to HFD-induced features of the metabolic syndrome and have increased lipolysis, energy expenditure, and thermogenesis, with an increase in core body temperature. <i>Yipf6</i><sup><i>KLZ/Y</i></sup> mice with hepatocyte-specific deletion of FGF21 were no longer protected from diet-induced obesity. We show that YIPF6 binds FGF21 in the endoplasmic reticulum to limit its secretion and specifies packaging of FGF21 into coat protein complex II (COPII) vesicles during development of obesity in mice. Levels of YIPF6 protein in human liver correlate with hepatic steatosis and correlate inversely with levels of FGF21 in serum from patients with nonalcoholic fatty liver disease (NAFLD). YIPF6 is therefore a newly identified regulator of FGF21 secretion during development of obesity and could be a target for treatment of obesity and NAFLD.
Reconstitution of immune cell interactions in free-standing membranes (2018)

The spatiotemporal regulation of signalling proteins at the contacts formed between immune cells and their targets determines how and when immune responses begin and end. Therapeutic control of immune responses therefore relies on thorough elucidation of the molecular processes occurring at these interfaces. However, the detailed investigation of each component's contribution to the formation and regulation of the contact is hampered by the complexities of cell composition and architecture. Moreover, the transient nature of these interactions creates additional challenges, especially in the use of advanced imaging technology. One approach that circumvents these problems is to establish <i>in vitro</i> systems that faithfully mimic immune cell interactions, but allow complexity to be 'dialled-in' as needed. Here, we present an <i>in vitro</i> system that makes use of synthetic vesicles that mimic important aspects of immune cell surfaces. Using this system, we began to explore the spatial distribution of signalling molecules (receptors, kinases and phosphatases) and how this changes during the initiation of signalling. The GUV/cell system presented here is expected to be widely applicable.
Erratum: “Atom probe analysis of interfacial abruptness and clustering within a single InxGa1−xN quantum well device on semipolar (101¯1¯) GaN substrate” [Appl. Phys. Lett. 98, 191903 (2011)] (2011)

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Lifetime Estimation of the Nanophosphate $\hbox{LiFePO}_{4}\hbox{/C}$ Battery Chemistry Used in Fully Electric Vehicles (2015)

There are currently many different lithium ion (Li-ion) chemistries available on the market, and several new players are in the research and development process; however, none of them is superior to the other chemistries in all aspects. Relatively low price, long cycle and calendar lifetime, and intrinsic safety of the nanophosphate LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> /C Li-ion chemistry make it possible to consider this chemistry for electric vehicle (EV) applications. This paper investigates the lifetime of the nanophosphate LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> /C battery chemistry when it is used for full electrical vehicles. The investigation is performed considering a semiempirical calendar and cycle lifetime model, which was developed based on extended accelerated lifetime tests. Both capacity and power capability degradations during calendar and cycle life aging are considered and quantified. Finally, the developed battery cell lifetime model is used to study the capacity and power capability degradation behavior of the tested nanophosphate LiFePO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> /C battery for two EV operational scenarios.
Participation of the Protein G o in Multiple Aspects of Behavior in C. elegans (1995)

The goa-1 gene encoding the alpha subunit of the heterotrimeric guanosine triphosphate-binding protein (G protein) Go from Caenorhabditis elegans is expressed in most neurons, and in the muscles involved in egg laying and male mating. Reduction-of-function mutations in goa-1 caused a variety of behavioral defects including hyperactive movement, premature egg laying, and male impotence. Expression of the activated Go alpha subunit (G alpha o) in transgenic nematodes resulted in lethargic movement, delayed egg laying, and reduced mating efficiency. Induced expression of activated G alpha o in adults was sufficient to cause these phenotypes, indicating that G alpha o mediates behavior through its role in neuronal function and the functioning of specialized muscles.
License-exempt LTE systems for secondary spectrum usage: Scenarios and first assessment (2011)

This paper investigates the feasibility and broad implications of the use of 3GPP LTE systems in license-exempt situations. License-exempt use can occur in traditional unlicensed bands or in secondary usage of white space spectrum. Various scenarios for license-exempt use are listed with a particular focus on spectrum access as a secondary user. Regulatory requirements devised by Federal Communications Commission (FCC) for TV white space usage are described and tabulated. General principles and recommendations for license exempt spectrum usage are proposed with some important scenarios being identified. Additional requirements arise out of the need to share the spectrum with other potential users in a fair manner. System simulation results in an indoor setting are used to estimate spectral efficiencies under such conditions. We conclude that LTE can be used in license-exempt secondary usage scenario with only minor modifications, such as fair sharing procedures, and could benefit from support for higher order modulations.
Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial. (2012)

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p&lt;0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common &gt; grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.
Potential Role of Immunosuppression in Therapeutic Effects Conferred by Cord Blood- Derived Mesenchymal Stem Cells. (2005)

Abstract Our previous studies consistently demonstrate enhanced neural protective effects of cord blood in comparison to stem cells from adult marrow. Similarly, cord blood possesses diminished immuno-stimulatory activity, and the basis of this effect has not been defined. Since neural damage may be potentiated by immune activation of inflammatory cascades, we examined the effects of cord blood-derived MSCs (mesenchymal stem cells) on immune responses. We isolated and characterized a population of cord blood MSCs. These cells maintained their pluripotency in culture. Progeny generated in the absence of differentiation were strongly adherent, did not express CD34, CD45, CD3, CD19 antigens, and did not generate hematopoietic colonies in methylcellulose. However, cultured cord blood MSCs possessed a remarkable ability to support the proliferation as well as the differentiation of hematopoietic cells in vitro. In addition, supernatants from cultured cord blood MSCs promoted survival of peripheral blood mononuclear cells cultured under conditions designed to induce cell stress and limit protein synthesis. We examined immune modulation by cord blood MSCs after co-culture with murine splenocytes. While spleen cells from normal C57Bl/6 mice exhibited a prominent IgM response after immunization with the T-cell dependent antigen, SRBCs, this response was significantly decreased after incubation with cord blood MSCs. Consistently, cord blood MSCs mitigated the enhanced mixed lymphocyte proliferative response C57Bl/6 T-cells exhibit when exposed to lymphocytes from non-related animals. To investigate whether these immune suppressive properties could be therapeutically useful in a transplantation model for autoimmune disease, cord blood MSCs were transplanted into sublethally irradiated BXSB mouse model for systemic lupus. Thirty days after infusion, defective IgM humoral immune responses of splenocytes of these mice normalized. This normalization paralleled normalization of the disrupted lymphoid cellularity observed in the spleens of diseased animals. Our results are consistent with the hypothesis that immune regulation is involved in the therapeutic utility of MSCs.
Towards Privacy-Preserving Ego-Motion Estimation Using an Extremely Low-Resolution Camera (2020)

Ego-motion estimation is a core task in robotic systems as well as in augmented and virtual reality applications. It is often solved using visual-inertial odometry, which involves using one or more always-on cameras on mobile robots and wearable devices. As consumers increasingly use such devices in their homes and workplaces, which are filled with sensitive details, the role of privacy in such camera-based approaches is of ever increasing importance. In this letter, we introduce the first solution to perform privacy-preserving ego-motion estimation. We recover camera egomotion from an extremely low-resolution monocular camera by estimating dense optical flow at a higher spatial resolution (i.e., 4x super resolution). We propose SRFNet for directly estimating Super-Resolved Flow, a novel convolutional neural network model that is trained in a supervised setting using ground-truth optical flow. We also present a weakly supervised approach for training a variant of SRFNet on real videos where ground truth flow is unavailable. On image pairs with known relative camera orientations, we use SRFNet to predict the auto-epipolar flow that arises from pure camera translation, from which we robustly estimate the camera translation direction. We evaluate our super-resolved optical flow estimates and camera translation direction estimates on the Sintel and KITTI odometry datasets, where our methods outperform several baselines. Our results indicate that robust ego-motion recovery from extremely low-resolution images can be viable when camera orientations and metric scale is recovered from inertial sensors and fused with the estimated translations.
Improving Tremor Detection and Quantification with Automated Measurements of Stroke Energy (P3.014) (2017)

To improve the efficiency and accuracy of tremor rating, by automating the detection and quantification of pen stroke energy as one aspect of tremor.
Scintillation Properties of Non-doped and Pr-doped BaO–B2O3–SiO2 Glasses and Glass-ceramics (2021)

We have studied the scintillation properties of non-doped and Pr-doped BaO-B 2 O 3 -SiO 2 glasses and glass-ceramics. The glass transition temperature (T g ), the temperature of crystallization onset (T x ), and the crystallization peak (T p ) were determined by differential thermal analysis. The glass-ceramics were obtained by heating at three different temperatures (T g + 50 C, T x , and T p ). We confirmed that the X-ray diffraction peaks can be ascribed to the BaSiO 3 crystalline phase in the glass-ceramic samples. In the X-ray-induced scintillation spectra, we observed the intrinsic luminescence of the host glass and luminescence due to the 4f-4f transition of Pr 3+ ions. In addition, the 1% Pr-doped BaO-B 2 O 3 -SiO 2 glass-ceramic with heating at T g + 50 C clearly showed luminescence in the wavelength range from 250 to 350 nm under X-ray excitation. Its photoluminescence (PL) decay time was estimated to be 26.28 ns and its luminescence is considered to be due to the 5f-4f transition of Pr 3+ ions.
Color Image Correlation For Spectral/Spatial Recognition (1989)

Through a slight modification of conventional monochromatic correlation, we formulate a color correlation which is capable of spectral and spatial recognition. Expressing RGB (red, green and blue) images, which are commonly used, in a vector form, the color correlation is decomposed of 9 terms, 3 intraband and 6 interband. To reduce the calculation time, we introduce preprocessings; projection onto appropriate plane and vector in RGB color space. The former one enables us to recognize an object with taking into account its both shape and color, and the latter one improves the sharpness of the cross-correlation peak. We also show the effectiveness of the color correlation applied to a quantitative measurement of stomach&apos;s surface from stereo endoscopic pictures.
Descending to the twilight-zone: changes in coral reef fish assemblages along a depth gradient down to 65 m (2008)

In contrast to the abundance of literature on the relationship between fish assemblages and habitat structure in the upper 30 m of coral reefs, the deeper (> 40 m) parts of coral reefs are rarely studied. We examined changes in reef fish diversity and habitat structure along an increasing depth gradient, including the unknown deep reef. We ran visual and video transects along a substantial depth gradient (0 to 65 m) in the northern Red Sea and extended the known depth distribution for 48 reef species. We found a change in assemblage composition highly correlated to both the depth gradient and a reduction in the abundance of branching corals with depth. The number of reef fish species declined with depth and we also measured a high species turnover as measured by beta diversity ( t , w ) in the deep reef. This pattern is mainly due to the replacement of the abundant damselfishes in the shallow reef, which prey on zooplankton, by zooplanktivorous sea basses and wrasses in the deep reef. The steep reduction in branching corals, which most damselfishes use for cover, may be the main factor contributing to this change. We found a peak in species richness (alpha diversity) at 30 m, a peak in w at 50 to 65 m, and peaks in t at 30 to 50 m and 50 to 65 m. The 30 m depth stratum shows species of both shallow and deep assemblages generating a transition zone with characters of both deep and shallow habitats. The fish assemblage continues to change with depth, and future research will determine if there exists a depth threshold at which the assemblage will stabilize.
Fatty Acid−Albumin Complexes and the Determination of the Transport of Long Chain Free Fatty Acids across Membranes (2004)

Understanding the mechanism that governs the transport of long chain free fatty acids (FFA) across lipid bilayers is critical for understanding transport across cell membranes. Conflicting results have been reported for lipid vesicles; most investigators report that flip-flop occurs within the resolution time of the method (<5 ms) and that dissociation from the membrane is rate limiting, while other studies find that flip-flop is rate limiting and on the order of seconds. We have reinvestigated this problem and find that the methods used in studies reporting rapid flip-flop have not been interpreted correctly. We find that accurate information about transport of FFA across lipid vesicles requires that FFA be delivered to the vesicles as complexes with albumin (BSA). For example, we find that stopped-flow mixing of uncomplexed FFA with small unilamellar vesicles (SUV) containing pyranine yields the very fast influx rates reported previously (>100 s(-1)). However, these influx rates increase linearly with lipid vesicle concentration and can therefore not, as previously interpreted, represent flip-flop. In contrast, measurements of influx rates in SUV and giant unilamellar vesicles performed with oleate-BSA complexes reveal no dependence on vesicle concentration and yield influx rate constants of approximately 4 and approximately 0.5 s(-1), respectively. Rate constants for efflux and dissociation were determined from the transfer of oleate from vesicles to BSA and reveal similar influx and efflux but dissociation rate constants that are approximately 5-10-fold greater. We conclude that flip-flop is rate limiting for transport of FFA across lipid vesicles and slows with an increasing radius of curvature. These results, in contrast to those reporting that flip-flop is extremely fast, indicate that the lipid bilayer portion of biological membranes may present a significant barrier to transport of FFA across cell membranes.
Comparison of carrier signal voltage and current injection for the estimation of flux angle or rotor position (2002)

The focus of this paper is on a comparative analysis of position, velocity, and flux estimation in AC machines based on the injection of a carrier signal superimposed on the fundamental excitation. Specifically the paper compares methods based on voltage and current injection and develops guidelines on their respective use. To provide a basis for fair comparison, the paper addresses two problems of carrier signal current injection: (1) the regulation of high frequency currents with current regulators of limited bandwidth (regulation of the carrier signals with zero steady-state error is necessary to avoid loss of spatial information); and (2) the extraction of the spatial information contained in the induced voltages.