gebhart/patrepeval huggingface dataset:
Insights into BAY 60-2770 Activation and S-Nitrosylation-Dependent Desensitization of Soluble Guanylyl Cyclase via Crystal Structures of Homologous Nostoc H-NOX Domain Complexes (2013)

The soluble guanylyl cyclase (sGC) is an important receptor for nitric oxide (NO). Nitric oxide activates sGC several hundred fold to generate cGMP from GTP. Because of sGC's salutary roles in cardiovascular physiology, it has received substantial attention as a drug target. The heme domain of sGC is key to its regulation as it not only contains the NO activation site but also harbors sites for NO-independent sGC activators as well an S-nitrosylation site (β1 C122) involved in desensitization. Here we report the crystal structure of the activator BAY 60-2770 bound to the Nostoc H-NOX domain that is homologous to sGC. The structure reveals that BAY 60-2770 has displaced the heme and acts as a heme mimetic via carboxylate-mediated interactions with the conserved YxSxR motif as well as hydrophobic interactions. Comparisons with the previously determined BAY 58-2667 bound structure reveal that BAY 60-2770 is more ordered in its hydrophobic tail region. sGC activity assays demonstrate that BAY 60-2770 has about 10% higher fold maximal stimulation compared to BAY 58-2667. S-Nitrosylation of the BAY 60-2770 substituted Nostoc H-NOX domain causes subtle changes in the vicinity of the S-nitrosylated C122 residue. These shifts could impact the adjacent YxSxR motif and αF helix and as such potentially inhibit either heme incorporation or NO-activation of sGC and thus provide a structural basis for desensitization.
Binocular Coordination and Interocular Balance in Amblyopia (2020)

Saccades are ballistic eye movements that humans make to direct gaze to an object of interest. When landing on a new fixation point, effective binocular coordination facilitates accurate convergence of the eyes, helping to fuse a single image. Without accurate convergence, a double image may be perceived. We have shown that the visual system uses statistical regularities in the natural environment to aid eye alignment at the end of saccades (Gibaldi & Banks,2019), defining the empirical oculomotor horopter. This behavior is consistent when stereovision is functional and effective. In this study we investigated whether the same statistical regularities are exploited in stereoanomolous binocular vision in amblyopia and strabismus. Nine subjects participated, six with normal vision and stereovision, and three with amblyopia (at least two lines difference between the eyes) and impaired stereovision (stereothreshold > 200arcmin). Subjects performed saccades to LED targets arranged vertically, while their eye movements were recorded with an Eyelink II eyetracker. We measured horizontal vergence after completion of monocular and binocular saccades to assess whether vergence is consistent with the natural-disparity distribution. We additionally measured perceptual interocular balance by asking observers to indicate the apparent location of dichoptic stimuli with interocular contrast differences. The oculomotor horopter of healthy subjects presents a consistent pattern of divergence for upward saccades and of convergence for downward saccades. This matches environmental scene statistics, and this effect is larger with monocular viewing. In two amblyopic subjects this pattern is not present, and vergence shows greater variability as compared to healthy subjects, demonstrating a lack of binocular coordination. Interestingly, the third amblyopic observer showed only a slight imbalance, which was accompanied by better binocular coordination. The evaluation of binocular coordination could be used for an objective assessment of binocular visual dysfunction, useful for screening young, non-collaborative patients and possibly early intervention.
Volpeet al.Reply: (2011)

A Reply to the Comment by R. Mannella and P. V. E. McClintock.Received 8 July 2011DOI:https://doi.org/10.1103/PhysRevLett.107.078902© 2011 American Physical Society
Tissue Engineering and Developmental Biology: Going Biomimetic (2006)

This article contains the collective views expressed at the first session of the workshop "Tissue Engineering--The Next Generation," which was devoted to the interactions between developmental biology and tissue engineering. Donald Ingber discussed the chasms between developmental biology and tissue engineering from the perspective of a cell biologist who has had interest in tissue engineering since its early days. Van C. Mow shared a historical perspective on the development of tissue engineering as one of the first engineers involved in the field. David Butler offered an assessment of functional tissue engineering, a new area he helped establish and promote. Laura Niklason discussed how to be more effective in developing cellular therapies for large numbers of patients. Johnny Huard described his approach to tissue engineering, based on the use of muscle-derived cells. Jeremy Mao focused on cell homing and cell density in the context of native development and relevance to tissue engineering. Ioannis Yannas proposed a set of "rules" in organ regeneration. Collectively, the faculty expressed a remarkable level of enthusiasm for bridging the gaps between developmental biology and tissue engineering and offered new ideas on how to facilitate the interaction between the two fields.
Genetically engineered CAR NK cells display selective cytotoxicity against FLT3‐positive B‐ALL and inhibit in vivo leukemia growth (2019)

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a promising effector cell type for adoptive cancer immunotherapy. Both, genetically modified donor-derived NK cells as well as continuously expanding NK-92 cells are currently under clinical development. To enhance their therapeutic utility for the treatment of pre-B-cell acute lymphoblastic leukemia (B-ALL), we engineered NK-92 cells by lentiviral gene transfer to express a FMS-like tyrosine kinase 3 (FLT3)-specific CAR that contains a composite CD28-CD3ζ signaling domain. FLT3 has primarily been described as a therapeutic target for acute myeloid leukemia, but overexpression of FLT3 has also been reported in B-ALL. Exposure of FLT3-positive targets to CAR NK-92 cells resulted in conjugate formation between NK and leukemia cells, NK-cell degranulation and selective cytotoxicity toward established B-ALL cell lines and primary blasts that were resistant to parental NK-92. In a SEM B-ALL xenograft model in NOD-SCID IL2R γ<sup>null</sup> mice, treatment with CAR NK-92 but not parental NK-92 cells markedly inhibited disease progression, demonstrating high antileukemic activity in vivo. As FLT3 is known to be also expressed on precursor cells, we assessed the feasibility of incorporating an inducible caspase-9 (iCasp9) suicide switch to enhance safety of our approach. Upon addition of the chemical dimerizer AP20187 to NK-92 cells coexpressing the FLT3-specific CAR and iCasp9, rapid iCasp9 activation was observed, precluding further CAR-mediated cytotoxicity. Our data demonstrate that B-ALL can be effectively targeted by FLT3-specific CAR NK cells which may complement CD19-directed immunotherapies, particularly in cases of inherent or acquired resistance to the latter.
COMPRENDO: Focus and Approach (2006)

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose-response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters--Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates) .
Measurement System for Evaluating Wanted and Unwanted Forces on a Point Absorbing Wave Energy Converter during Offshore Operation (2015)

A force measurement system has been developed and installed in awave energy converter at Uppsala University. The force in theconnection line as well as the vertical and horizontal strain in thegenerator hull is measured. With these measurements the forces actingon the generator during offshore operation can be monitored andanalyzed. This paper presented the principle, implementation and testresults of the measurement system. A brief discussion of error sourcesand possible improvements is also given.
A new approach to DNS security (DNSSEC) (2001)

The Domain Name System (DNS) is a distributed database that allows convenient storing and retrieving of resource records. DNS has been extended to provide security services (DNSSEC) mainly through public-key cryptography. We propose a new approach to DNSSEC that may result in a significantly more efficient protocol. We introduce a new strategy to build chains of trust from root servers to authoritative servers. The techniques we employ are based on symmetric-key cryptography.
Modeling of Electrochemical Impedance Data of a Magnesium-Rich Primer (2008)

The application of Mg-rich primers (MRPs) for the protection of aluminum structures represents an attractive alternate to the environmentally unfriendly Cr-rich primers that are presently used. The protective modes of MRPs are similar to those of Zn-rich primers (ZRPs) on steel and include cathodic protection driven by the more active Mg particles compared to the Al substrate and a barrier-type protection due to the insulation of the substrate from the environment. Interpretation of ZRP electrochemical impedance spectroscopy (EIS) data has been accomplished using a transmission-line model that accounted for the contact impedance between the zinc particles, the impedance associated with the zinc dissolution, and the percolation resistance of the coating. EIS experiments results are presented here for an MRP on a gold substrate under immersion in dilute Harrison's solution. The data were analyzed using the measurement model technique to determine the consistency with respect to Kramer–Kronig relationships. The transmission-line model was used to analyze the data to demonstrate their applicability for analyzing the protection afforded by the MRP. Gold was used as a noble substrate and to promote that the electromotive degradation of the MRP as the mixed potential of an MPR/gold system was more positive than that of an MRP/Al system.
Formation of Keteniminium Salts: Mechanistic Aspects andSubstituent Effects (2022)

Keteniminium salts (KIs) are versatile intermediates in synthetic organic chemistry. Elucidation of the mechanistic aspects of KI formation reactions facilitates the design of KI intermediates that give access to complex compounds. In this study, in order to provide a comprehensive understanding of KI formation, various mechanisms were investigated using a density functional theory approach. Particularly, Ghosez’s KI formation mechanism, by activation of an amide with triflic anhydride, was extensively elaborated, since this procedure occurs under mild conditions and is, by far, the most frequently used method. Moreover, a broad range of substituents was examined to give insight on their potential contributions to the ease of formation of KIs. The effect of substituents on the reactivity of the corresponding starting amides was inspected by means of energetics, population analysis, frontier molecular orbitals (FMO) and reactivity descriptors. Computed data shows that electron donating groups lower the activation barrier by increasing the electron density of the amide carbonyl oxygen. Additionally, distortion/interaction model also confirmed the energetic outcomes. In addition, investigation of KI reactivity using FMO, and reactivity descriptors displayed that KI reactivity is inversely correlated with amide reactivity. Lastly, experimental outcomes are in line with computational predictions. We suggest that the reactivity of the amide has a crucial impact on the ease of KI formation and the reactivity of the corresponding KIs. This study gives pivotal insights into mechanistic aspects of KI formation and the role of the substituents.
High-Performance and Stable Transparent Hf–In–Zn–O Thin-Film Transistors With a Double-Etch-Stopper Layer (2010)

Transparent hafnium indium zinc oxide thin-film transistors adopting single- and double-etch-stopper layers were evaluated. Compared to devices with a single <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\hbox{SiO}_{x}$</tex></formula> etch stopper (ES) grown at 150 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$^{\circ}\hbox{C}$</tex></formula> , a double ES with a second <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\hbox{SiO}_{x}$</tex></formula> film grown at 350 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$^{\circ}\hbox{C}$</tex></formula> provides a superior device performance such as improved subthreshold swing, threshold voltage, field effect mobility, and higher stability under a negative bias stress. The stretched-exponential analyses of the bias stress results indicate that the denser high-temperature <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\hbox{SiO}_{x}$</tex></formula> protects more effectively the underlying semiconductor during the source/drain etch process and suppresses the generation of defect states therein.
Stages in the Progression of HIV Infection in Chimpanzees (1987)

Circulating HIV antigens and HIV specific antibodies in sera of experimentally infected chimpanzees were monitored by ELISA immunoassay, Western blot, and radioimmunoprecipitation procedures. Three of three chimpanzees given plasma from patients with AIDS or ARC tested positive for HIV antigens beginning six to ten weeks after transfusion. Antigen production rose sharply but was of short duration. Despite their proven infectivity and the presence of anti-HIV antibody, all donors to these chimpanzees tested negative for the HIV antigen. Of the three animals that developed HIV antigen one animal did not produce any HIV antibodies or evidence of disease. A second produced antibodies to only the p24 and p18 antigens and remained clinically well. The third produced antibodies beginning with anti-p24, to all the major HIV proteins except gp120, and then developed marked lymphadenopathy which persisted for 32 weeks. Antibody persistence after the disappearance of clinical disease was variable and was greatest for gp41 and least for p24. These data may be of value in the interpretation of human serological testing for HIV and in further studies of the sequence of events leading to the pathological effects of HIV infection. A significant value of the chimpanzee model is the capacity of this animal to respond in a variety of ways to HIV infection, suggesting the existence of successive or alternate states of early HIV infection, and may have implications in the design of early interventions.
P4‐016: MONITORING TAU PATHOLOGY AND MONOCLONAL ANTIBODIES IN VIVO BY TWO‐PHOTON IMAGING (2014)

Studies from our laboratory and more recently several others have demonstrated the efficaciousness of tau immunotherapy. We have developed a monoclonal antibody, 4E6G7, targeting the pSer-396/404 tau epitope. It has been shown to enter neurons and reduce hyperphosphorylated tau in ex vivo brain slice cultures, as well as clear tau aggregates and improve cognition in vivo. Additionally, the specific uptake of 4E6G7 by neurons with tau pathology is dependent on its Fc region. Here, using in vivo two-photon imaging, we investigated the uptake and dynamics of 4E6G7 in live transgenic taupathy mice. Aged htau mice (15-18 months) were injected intravenously with FSB (for labeling tau aggregates, 0.05%, 300 μL), and Alexa-568 labeled 4E6G7 or its Fab fragment (200 μg). A small region of the skull was thinned to 10-20 μm thickness for two-photon imaging at 1, 4, and 7 days after injection. Strong signals of both FSB and 4E6G7 were detected in cortical neurons one day after injection, with a high degree of colocalization. Compared to the whole antibody, substantially more of its Fab fragment was taken up by FSB-negative neurons (81% vs. 61% colocalization with FSB, p<0.05). Cortical antibody signal was quite stable during the imaging period (96% at day 4, 72% at day 7), whereas most of Fab fragments disappeared after a few days (37% at day 4, 28% at day 7, p<0.01 compared to whole antibody on respective days). FSB signal decreased gradually to 63% with antibody and 56% with Fab. However, at this point, we cannot distinguish whether it resulted from clearance of tau pathology or degradation of the dye. Hopefully, a more detailed mapping of these signals compared to post mortem analyses of brain tissue will clarify if intracellular tau antibodies promote clearance of tau aggregates. By two-photon imaging of live transgenic mice, we confirmed the ability of tau antibodies to enter brain tissue and specifically bind to tau aggregates. The Fc region of the antibody was required for selectively targeting intraneuronal tau pathology. Decrease in FSB signal over time suggests that tau aggregates may be cleared but requires confirmation with more detailed analyses.
A study on the effective interconnection method between base stations and selector bank subsystem in CDMA cellular networks (2002)

A CDMA cellular land network (CCLN) consists of base stations connected to a selector bank subsystem. In the case of considering only the voice traffic, CCLN can be designed based on E1/T1 physical line and HDLC protocol with fixed or variable length. However, it is necessary to support not only voice but also data traffic in the CDMA cellular system. Thus, it is necessary to use physical lines efficiently to increase bandwidth efficiency and transmission speed. However, the conventional CCLN has some problems in that the bandwidth is wasted because each BTS has its own private line. In this paper, a method using DQDB MAN as a CDMA interconnect subsystem (CIS) is considered, and the performances of the conventional and proposed method are analyzed by computer simulation. According to the simulation results, if the traffic from all mobile stations is uniformly distributed among all BTS's, the performances of both the conventional and proposed methodologies turn out to be almost equal. However, the performance of the methodology using the DQDB MAN is much better than that of the conventional method, in the case that the traffic from all mobile stations is nonuniformly distributed.
Conformationally Constrained Analogues of Diacylglycerol. 24. Asymmetric Synthesis of a Chiral (R)-DAG-Lactone Template as a Versatile Precursor for Highly Functionalized DAG-Lactones (2004)

[structure: see text] Commercially available 2-methylenepropane-1,3-diol was converted to chiral epoxide (R)-2 via Sharpless asymmetric epoxidation in >96% ee. Regiospecific epoxide ring opening and reduction of the intermediate alkyne set the stage for a one-pot lactonization to give (R)-6, a convenient precursor for all functionalized chiral DAG-lactones used as potent PK-C ligands. The synthesis of the most potent DAG-lactones known to date, (Z)-10 and (E)-10, served to confirm PK-C's exclusive preference for the (R)-stereochemistry in this class of compounds.
Surgical Exposure for Open Reduction and Internal Fixation or Prosthetic Replacement of the Radial Head (2002)

Displaced radial head fractures can be successfully treated with open reduction and internal fixation in many cases. Radial head fractures that are too comminuted or osteoporotic to achieve stable internal fixation should be treated with alternative techniques, such as radial head excision or radial head arthroplasty. Exposure of the radial head and neck, without compromise of elbow stability, can be obtained by the method described in this article.
Sequential Electron−Proton−Electron Transfer in the Radiolytic and Photochemical Oxidation of Thioxanthene and Xanthene (1996)

Radical cations generated from thioxanthene and xanthene undergo structural relaxation in low-temperature hydrocarbon glasses upon warming. Under conditions of unrestricted diffusion, deprotonation of the radical cations occurs and results in the formation of the thioxanthyl and xanthyl radicals. Subsequent electron loss leads ultimately to the closed-shell thioxanthyl and xanthyl cations. Using combined steady-state and time-resolved radiolytic and photochemical methods, the radical cations, radicals, and cations of interest were spectroscopically and kinetically characterized.
Comparison between hexa- and conventional E-type core three-phase transformers (2008)

The concept of power transformer design with a symmetric core construction (the hexa-transformer) provides a more compact solution compared to traditional technology based on an E-type core. This paper evaluates parameters of two 100 kVA three-phase transformers built according to both concepts. The evaluation includes calculations of induced voltages, inductances, core losses and weight differences. Further, the calculated parameters are compared with measured values. It is shown that, for the investigated transformer size and ratings, the compact design of the hexa-transformer yields up to 25% lower core losses, 40% smaller magnetization current and 12% lower core weight compared to the conventional E-core transformer.
High-Frequency EPR and ENDOR Spectroscopy of Mn2+ Ions in CdSe/CdMnS Nanoplatelets (2023)

Semiconductor colloidal nanoplatelets based of CdSe have excellent optical properties. Their magneto-optical and spin-dependent properties can be greatly modified by implementing magnetic Mn<sup>2+</sup> ions, using concepts well established for diluted magnetic semiconductors. A variety of magnetic resonance techniques based on high-frequency (94 GHz) electron paramagnetic resonance in continuous wave and pulsed mode were used to get detailed information on the spin structure and spin dynamics of Mn<sup>2+</sup> ions in core/shell CdSe/(Cd,Mn)S nanoplatelets. We observed two sets of resonances assigned to the Mn<sup>2+</sup> ions inside the shell and at the nanoplatelet surface. The surface Mn demonstrates a considerably longer spin dynamics than the inner Mn due to lower amount of surrounding Mn<sup>2+</sup> ions. The interaction between surface Mn<sup>2+</sup> ions and <sup>1</sup>H nuclei belonging to oleic acid ligands is measured by means of electron nuclear double resonance. This allowed us to estimate the distances between the Mn<sup>2+</sup> ions and <sup>1</sup>H nuclei, which equal to 0.31 ± 0.04, 0.44 ± 0.09, and more than 0.53 nm. This study shows that the Mn<sup>2+</sup> ions can serve as atomic-size probes for studying the ligand attachment to the nanoplatelet surface.