gebhart/patrepeval huggingface dataset:
Progress in Confocal Laser Endomicroscopy for Neurosurgery and Technical Nuances for Brain Tumor Imaging With Fluorescein (2019)

<b>Background:</b> Previous studies showed that confocal laser endomicroscopy (CLE) images of brain tumors acquired by a first-generation (Gen1) CLE system using fluorescein sodium (FNa) contrast yielded a diagnostic accuracy similar to frozen surgical sections and histologic analysis. We investigated performance improvements of a second-generation (Gen2) CLE system designed specifically for neurosurgical use. <b>Methods:</b> Rodent glioma models were used for <i>in vivo</i> and rapid <i>ex vivo</i> CLE imaging. FNa and 5-aminolevulinic acid were used as contrast agents. Gen1 and Gen2 CLE images were compared to distinguish cytoarchitectural features of tumor mass and margin and surrounding and normal brain regions. We assessed imaging parameters (gain, laser power, brightness, scanning speed, imaging depth, and Z-stack [3D image acquisition]) and evaluated optimal values for better neurosurgical imaging performance with Gen2. <b>Results:</b> Efficacy of Gen1 and Gen2 was similar in identifying normal brain tissue, vasculature, and tumor cells in masses or at margins. Gen2 had smaller field of view, but higher image resolution, and sharper, clearer images. Other advantages of the Gen2 were auto-brightness correction, user interface, image metadata handling, and image transfer. CLE imaging with FNa allowed identification of nuclear and cytoplasmic contours in tumor cells. Injection of higher dosages of FNa (20 and 40 mg/kg vs. 0.1-8 mg/kg) resulted in better image clarity and structural identification. When used with 5-aminolevulinic acid, CLE was not able to detect individual glioma cells labeled with protoporphyrin IX, but overall fluorescence intensity was higher (<i>p</i> < 0.01) than in the normal hemisphere. Gen2 Z-stack imaging allowed a unique 3D image volume presentation through the focal depth. <b>Conclusion:</b> Compared with Gen1, advantages of Gen2 CLE included a more responsive and intuitive user interface, collection of metadata with each image, automatic Z-stack imaging, sharper images, and a sterile sheath. Shortcomings of Gen2 were a slightly slower maximal imaging speed and smaller field of view. Optimal Gen2 imaging parameters to visualize brain tumor cytoarchitecture with FNa as a fluorescent contrast were defined to aid further neurosurgical clinical <i>in vivo</i> and rapid <i>ex vivo</i> use. Further validation of the Gen2 CLE for microscopic visualization and diagnosis of brain tumors is ongoing.
The Main-Chain Oxygen: Unappreciated Effects on Peptide and Protein Structure (2015)

Current limitations in protein structure prediction and design suggest an incomplete understanding of the forces governing protein folding. As such, noncovalent interactions in proteins, particularly hydrogen bonds, have received great attention [1,2]. In common secondary structure patterns like the α-helix and β-sheet, main-chain N–H hydrogen bond donors approach their carbonyl acceptors approximately along the carbonyl bond axis [3], despite conventional wisdom that hydrogen bond energies are maximized when donors approach at 120° to the carbonyl bond axis [4]. This observation can be rationalized using a modern, quantummechanically based model of the carbonyl lone pairs that indicates that the two orbitals differ from the sp-hybridized VSEPR “rabbit ears” assumed commonly. Specifically, one lone pair, approximately sp-hybridized, is oriented along the carbonyl bond axis, while the second, purely p-orbital orients orthogonally (Figure 1). Canonical hydrogen bonds in protein secondary structure therefore often employ the s-rich lone pair; however, the role of the p-type lone pair is less clear. We have previously noted that backbone n→π* interactions are well poised to exploit this p-type lone pair [5]. In an n→π* interaction, the filled p-type lone pair of a carbonyl oxygen interacts with the empty π* orbital of an adjacent carbonyl group, and the mixing of these orbitals releases energy. These interactions have energies generally greater than 0.27 kcal/mol each [6], and are ubiquitous in folded proteins [7,8], particularly in the α-helix [9]. Yet, no analogous role for the p-type carbonyl lone pair has been identified in β-sheets. We now posit that a previously unappreciated hydrogen bond occurs within the backbone of individual residues in β-sheets.
Identification of in vivo brain-derived neurotrophic factor-stimulated autophosphorylation sites on the TrkB receptor tyrosine kinase by site-directed mutagenesis. (1994)

Brain-derived neurotrophic factor (BDNF) interacts with the TrkB receptor tyrosine kinase, the tyrosine kinase domain of which has homology with the insulin receptor subfamily of protein kinases. This includes the conservation of three regulatory tyrosines (residues 670, 674, and 675) known to play a crucial role in signal transmission by the insulin receptor (tyrosines 1158, 1162, and 1163). Wild-type TrkB and TrkB mutants with Y670F, Y674F/Y675F, Y751F (the tyrosine reported to be important in phosphatidylinositol 3-kinase binding (Obermeier, A., Lammers, R., Wiesmuller, K. H., June, G., Schlessinger, J., and Ullrich, A. (1993) J. Biol. Chem. 268, 22963-22966)), and K540R (consensus ATP binding lysine) substitutions were transiently expressed in COS cells for analysis of phosphorylation sites by two-dimensional phosphopeptide mapping. TrkB phosphorylation sites were also studied in MG86 cells stably expressing wild-type TrkB. In addition, the mutants were expressed in Chinese hamster ovary cells for analysis of the ability of the receptor to mediate BDNF-stimulated transcription from a 12-O-tetradecanoylphorbol-13-acetate response element (TRE). BDNF stimulated the phosphorylation of wild-type TrkB on multiple tyrosine and serine residues. This phosphorylation occurred on tyrosines 670, 674, and 675 plus two other tyrosines and at least two serines that were not unequivocally identified. Wild-type TrkB mediated a pronounced stimulation of TRE-dependent transcription. A Y674F/Y675F, but not Y670F, substitution dramatically inhibited this response. Surprisingly, in COS cells, a Y751F substitution induced dramatically lower tyrosine and serine phosphorylation at all sites but mediated a normal BDNF-stimulated activation of a TRE. Our results demonstrate a critical role for the phosphorylation of tyrosines 674 and 675 in BDNF-dependent signaling by wild-type TrkB.
Influence of visual cortical GABA concentration on perceptual suppression and binocular summation in amblyopia (2017)

Amblyopia is characterized by reduced visual acuity due to abnormal early visual experience and is often accompanied by suppression of signals from the amblyopic eye. Recent studies indicate a role for intracortical GABAergic inhibition in amblyopic suppression as well as a link between occipital GABA levels and fMRI visual cortical response amplitudes in healthy individuals. To better understand the relationships among behavioral suppression, GABA, and visual responses, we measured several types of perceptual suppression, visual cortical GABA levels with magnetic resonance spectroscopy (MRS), and fMRI response amplitudes in amblyopes and healthy controls. Specifically, we obtained the magnitude of surround suppression, overlay suppression, and interocular suppression for each participant using well-established psychophysical approaches. Additionally, we recorded fMRI activity in retinotopically-defined early visual cortical areas for four stimulus conditions: binocular, dichoptic (different stimuli in both eyes), and monocular stimulation of either the amblyopic/non-dominant or non-amblyopic/dominant eye. Finally, MRS was performed without visual stimulation to measure resting GABA concentration in bilateral occipital cortex. As expected, we found increased surround suppression in amblyopes when the target was presented to the amblyopic eye and the surround to the non-amblyopic eye, relative to the reverse stimulus configuration and to interocular surround suppression in controls. We quantified binocular summation of fMRI responses by computing the difference between binocular versus monocular and between binocular versus dichoptic response amplitudes. Amblyopes exhibited less fMRI binocular summation than controls for both metrics, and these measures of binocular summation were inversely correlated with visual cortical GABA concentration. Surprisingly, especially given our findings of increased perceptual suppression in amblyopia, visual cortical GABA levels were significantly lower in amblyopes than controls. Ongoing analyses are focused on correlating behavioral metrics of interocular interactions and perceptual suppression obtained from psychophysical data with visual cortical GABA levels and with fMRI response amplitudes in visual cortex. Meeting abstract presented at VSS 2017
Search for new physics in final states with two opposite-sign, same-flavor leptons, jets, and missing transverse momentum in pp collisions at s = 13 $$ \sqrt{s}=13 $$ TeV (2016)

A search is presented for physics beyond the standard model in final states with two opposite-sign, same-flavor leptons, jets, and missing transverse momentum. The data sample corresponds to an integrated luminosity of 2.3 fb -1 of proton-proton collisions at s = 13 TeV collected with the CMS detector at the LHC in 2015. The analysis uses the invariant mass of the lepton pair, searching for a kinematic edge or a resonant-like excess compatible with the Z boson mass. Both search modes use several event categories in order to increase the sensitivity to new physics. These categories are based on the rapidity of the leptons, the multiplicity of jets and b jets, the scalar sum of jet transverse momenta, and missing transverse momentum. The observations in all signal regions are consistent with the expectations from the standard model, and the results are interpreted in the context of simplified models of supersymmetry.
An Ultra-Area-Efficient 1024-Point In-Memory FFT Processor (2019)

Current computation architectures rely on more processor-centric design principles. On the other hand, the inevitable increase in the amount of data that applications need forces researchers to design novel processor architectures that are more data-centric. By following this principle, this study proposes an area-efficient Fast Fourier Transform (FFT) processor through in-memory computing. The proposed architecture occupies the smallest footprint of around 0.1 mm 2 inside its class together with acceptable power efficiency. According to the results, the processor exhibits the highest area efficiency ( FFT / s / area ) among the existing FFT processors in the current literature.
Forecasting Clinical Dose–Response From Preclinical Studies in Tuberculosis Research: Translational Predictions With Rifampicin (2018)

A crucial step for accelerating tuberculosis drug development is bridging the gap between preclinical and clinical trials. In this study, we developed a preclinical model-informed translational approach to predict drug effects across preclinical systems and early clinical trials using the in vitro-based Multistate Tuberculosis Pharmacometric (MTP) model using rifampicin as an example. The MTP model predicted rifampicin biomarker response observed in 1) a hollow-fiber infection model, 2) a murine study to determine pharmacokinetic/pharmacodynamic indices, and 3) several clinical phase IIa early bactericidal activity (EBA) studies. In addition, we predicted rifampicin biomarker response at high doses of up to 50 mg/kg, leading to an increased median EBA<sub>0-2 days</sub> (90% prediction interval) of 0.513 log CFU/mL/day (0.310; 0.701) compared to the standard dose of 10 mg/kg of 0.181 log/CFU/mL/day (0.076; 0.483). These results suggest that the translational approach could assist in the selection of drugs and doses in early-phase clinical tuberculosis trials.
A Multi-System Approach Assessing the Interaction of Anticonvulsants with P-gp (2013)

30% of epilepsy patients receiving antiepileptic drugs (AEDs) are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3) were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp) of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp) but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.
Two kinesin-like proteins mediate actin-based chloroplast movement in Arabidopsis thaliana (2010)

Organelle movement is essential for efficient cellular function in eukaryotes. Chloroplast photorelocation movement is important for plant survival as well as for efficient photosynthesis. Chloroplast movement generally is actin dependent and mediated by blue light receptor phototropins. In Arabidopsis thaliana, phototropins mediate chloroplast movement by regulating short actin filaments on chloroplasts (cp-actin filaments), and the chloroplast outer envelope protein CHUP1 is necessary for cp-actin filament accumulation. However, other factors involved in cp-actin filament regulation during chloroplast movement remain to be determined. Here, we report that two kinesin-like proteins, KAC1 and KAC2, are essential for chloroplasts to move and anchor to the plasma membrane. A kac1 mutant showed severely impaired chloroplast accumulation and slow avoidance movement. A kac1kac2 double mutant completely lacked chloroplast photorelocation movement and showed detachment of chloroplasts from the plasma membrane. KAC motor domains are similar to those of the kinesin-14 subfamily (such as Ncd and Kar3) but do not have detectable microtubule-binding activity. The C-terminal domain of KAC1 could interact with F-actin in vitro. Instead of regulating microtubules, KAC proteins mediate chloroplast movement via cp-actin filaments. We conclude that plants have evolved a unique mechanism to regulate actin-based organelle movement using kinesin-like proteins.
Ion Pairs of Weakly Coordinating Cations and Anions: Synthesis and Application for Sulfide to Sulfoxide Oxidations (2014)

Abstract A series of salts containing the weakly coordinating cations (WCC) 1-butyl-3-methylimidazolium ([Bmim] + ), 1-butyl-2,3-dimethylimidazolium ([Bdmim] + ), 1-dodecyl-3-methylimidazolium ([C 12 mim] + ), tetrabutylphosphonium ([PBu 4 ] + ), tributyltetradecylphosphonium ([P 4;4;4;14 ] + ), tetrabutylammonium ([NBu 4 ] + ), and 1,1,3,3-tetramethylguanidium ([TMG] + ) and fluorinated tetraarylborate anions of the type [B(Ar F ) 4 ] (Ar F =C 6 F 5 , C 6 H 3 -3,5-(CF 3 ) 2 ) were synthesized and characterized. The influence of cations and anions on the physical properties of the obtained compounds was examined. In case of the compound [TMG][B(C 6 F 5 ) 4 ] hydrogen-fluorine contacts between cation and anion are present in the solid state. Owing to H···F contacts between hydrogen peroxide and the fluorine substituents of the anion and the resulting activation of H 2 O 2 in solution, the compound [P 4;4;4;14 ][B(C 6 H 3 -3,5-(CF 3 ) 2 ) 4 ] is applicable as an efficient mediator for the oxidation of sulfides to sulfoxides
A silicon-glass hybrid lens for simultaneous color-and-thermal imaging (2013)

We show that color and thermal images from the same viewpoint and of the same view angle can be taken using a silicon-glass hybrid lens that focuses visible and far-infrared (FIR) light. The lens was fabricated using silicon three-dimensional fabrication process. Color and thermal images were taken with the hybrid lens. The maximum and mean differences of the color and thermal image displacements were 0.42 mm and 0.26 mm, respectively. The maximum and mean values of the differences in angle were 2.0° and 1.2°, respectively.
Imidazole-Linked Crystalline Two-Dimensional Polymer with Ultrahigh Proton-Conductivity (2019)

Proton-exchange membrane fuel cells are promising energy devices for a sustainable future due to green features, high power density, and mild operating conditions. A facile proton-conducting membrane plays a pivotal role to boost the efficiency of fuel cells, and hence focused research in this area is highly desirable. Major issues associated with the successful example of Nafion resulted in the search for alternate proton conducting materials. Even though proton carrier loaded crystalline porous organic frameworks have been used for proton-conduction, the weak host-guest interactions limited their practical use. Herein, we developed a crystalline 2D-polymer composed of benzimidazole units as the integral part, prepared by the condensation of aryl acid and diamine in polyphosphoric acid medium. The imidazole linked-2D-polymer exhibits ultrahigh proton conductivity (3.2 × 10<sup>-2</sup> S cm<sup>-1</sup>) (at 95% relative humidity and 95 °C) in the pristine state, which is highest among the undoped porous organic frameworks so far reported. The present strategy of a crystalline proton-conducting 2D-polymer will lead to the development of new high performing crystalline solid proton conductor.
Kinetics of cross-linking and de-cross-linking of EPM rubber with thermoreversible Diels-Alder chemistry (2017)

The kinetics of the Diels-Alder (DA) cross-linking and retro-Diels-Alder (rDA) de-cross-linking reactions have been studied for furan-containing EPM rubber thermoversibly cross-linked with a bismaleimide. Cross-linking conversions obtained from spectroscopic methods deviate from rheological methods as the former take into consideration both the intermediate DA adduct and complete cross-links, while the latter only determine the formation and decomposition of complete cross-links. The thermoreversibility of the system was shown by a combination of equilibrium swelling and rheological measurements. Dynamic time sweeps of the rubber at different temperatures were used to determine the Arrhenius activation energies of 7.04 and 57.9 kJ/mol for the DA and the rDA reactions, respectively. E a,DA is relatively low and suggests a diffusion limitation while E a,rDA correspond to values reported in literature. Both values were used to simulate cross-link density profiles as a function of time and temperature that correspond well with the experimental data.
Microring resonator-based diamond optothermal switch: a building block for a quantum computing network (2013)

The negatively-charged nitrogen-vacancy centers in diamond has motivated many groups building scalable quantum information processors based on diamond photonics. This is owning to the long-lived electronic spin coherence and the capability for spin manipulation and readout of NV centers.<sup>1-4</sup> The primitive operation is to create entanglement between two NV centers, based on schemes such as 'atom-photon entanglement' proposed by Cabrillo <i>et al</i>.<sup>5</sup>To scale this type of scheme beyond two qubits, one important component is an optical switch that allows light emitted from a particular device to be routed to multiple locations. With such a switch, one has choices of routing photons to specified paths and has the benefit of improving the entanglement speed by entangling multiple qubits at the same time. Yield of the existing diamond cavities coupled with NV centers are inevitably low, due to the nature of randomness for NV placement and orientation, variation of spectral stability, and variation of cavity resonance frequency and quality factor. An optical switch provides the capability to tolerate a large fraction of defective devices by routing only to the working devices. Many type of switching devices were built on conventional semiconductor materials with mechanisms from mechanical, thermal switching to carrier injection, photonics crystal, and polymer refractive index tuning .<sup>6-8</sup> In this paper, we build an optical-thermal switch on diamond with micro-ring waveguides, mainly for the simplicity of the diamond fabrication. The the switching function was realized by locally tuning the temperature of the diamond waveguides. Switching efficiency of 31% at 'drop' port and 73% at 'through' port were obtained.
Natural History of Friedreich Ataxia (2022)

The understanding of the diversity within FRDA populations and their patterns of functional decline provides an essential foundation for future clinical trial design including patient selection and facilitates the interpretation of the clinical relevance of progression detected in FRDA.
Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors (2011)

Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00428597.).
HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs (2023)

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIV<sup>neg</sup>) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin<sup>-</sup> BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIV<sup>neg</sup> individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIV<sup>posEVs</sup>) and plasma depleted of EVs (HIV PL<sup>depEVs</sup>). HIV<sup>posEVs</sup>, but not HIV PL<sup>depEVs</sup> or HIV<sup>negEVs</sup> (EVs from HIV<sup>neg</sup> individuals), increased atherosclerosis in <i>apoE</i><sup>-/-</sup> mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin<sup>-</sup> BMCs. Small RNA-seq identified EV-miRs overrepresented in HIV<sup>posEVs</sup>, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIV<sup>posEVs</sup> in vivo. Lin<sup>-</sup> BMCs overexpressing <i>Hmga2</i> (a let-7b-5p target gene) lacking the 3'UTR and as such is resistant to miR-mediated regulation showed protection against HIV<sup>posEVs</sup>-induced changes in lin<sup>-</sup> BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.