gebhart/patrepeval huggingface dataset:
Targeting EGFR in glioblastoma with a novel brain-penetrant small molecule EGFR-TKI (2021)

Summary Epidermal growth factor receptor (EGFR) is mutated or amplified in a majority of glioblastoma (GBM), and its mutation and focal amplification correlate with a more aggressive disease course. However, EGFR-directed tyrosine kinase inhibitors (TKIs) tested to date have yielded minimal clinical benefit. Here, we report a novel covalent-binding EGFR-TKI, CM93, as a potential drug to target adult GBMs with aberrant EGFR. CM93 has extraordinary brain exposure, with a brain-to-plasma ratio greater than 20-fold at estimated steady state. While all approved EGFR-TKIs are subject to extensive efflux transporter activity, CM93 does not inhibit the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporters in Caco-2 cells at expected clinically relevant plasma concentrations. Equally, CM93 demonstrates moderate absorption and permeation in Caco-2 cell monolayers with efflux ratios &lt; 2, suggesting that it is not likely a substrate of an efflux transporter. Collectively, these in vitro data may account for the dramatic increase in brain exposure over plasma as noted above. Pre-clinical efficacy studies showed that CM93 is more effective than other EGFR-TKIs in blocking the proliferation of GBM tumor cells from both patient-derived and cultured human GBM cell lines with EGFR amplification and/or EGFRvIII mutation. In addition, CM93 administered as a single agent was able to attenuate the growth of orthotopic U251-EGFRvIII xenografts and extend the survival of tumor-bearing mice in a dose-dependent manner. Moreover, CM93 inhibited EGFR phosphorylation in GBM tumors derived from a novel genetically-engineered mouse (GEM) model of GBM with EGFRvIII expression both in vitro and in vivo . CM93 also extended the survival of mice bearing orthotopic allografts of GBM. Notably, mice maintained stable body weight during treatments with increasing doses of CM93 up to 75 mg/kg per day. Together, these data suggest that CM93 is a potential EGFR-TKI well suited for the treatment of adult GBM with mutant EGFR.
Multifunctional Nanoparticles for Drug Delivery and Molecular Imaging (2013)

Recent advances in nanotechnology and growing needs in biomedical applications have driven the development of multifunctional nanoparticles. These nanoparticles, through nanocrystalline synthesis, advanced polymer processing, and coating and functionalization strategies, have the potential to integrate various functionalities, simultaneously providing (a) contrast for different imaging modalities, (b) targeted delivery of drug/gene, and (c) thermal therapies. Although still in its infancy, the field of multifunctional nanoparticles has shown great promise in emerging medical fields such as multimodal imaging, theranostics, and image-guided therapies. In this review, we summarize the techniques used in the synthesis of complex nanostructures, review the major forms of multifunctional nanoparticles that have emerged over the past few years, and provide a perceptual vision of this important field of nanomedicine.
MicroRNAs and Discovery of New Targets (2008)

MicroRNAs are endogenous short non-coding RNAs that regulate gene expression mainly at the post-transcriptional level by base pairing to the 3′ untranslated region of target messenger RNAs. At present, hundreds of microRNAs have been identified in humans, and some of them have been revealed to play a critical role especially in the initiation, progression, and malignant potential of various cancers. In this chapter, we discuss the role of microRNAs in cancer and its potential application for cancer therapy.
Total internal reflection for illumination and displays (2006)

Total internal reflection (TIR) can occur when a light ray traveling in a transparent material encounters an interface with another transparent, but less optically dense material. The phenomenon is interesting not only because the reflection can be close to perfect, but because the effect depends critically on the angle of incidence. Although TIR is used widely, in this article we discuss two less well known applications with which we have considerable experience. The first example is a device known as a prism light guide, a hollow dielectric structure that can transport a large luminous flux for illuminating engineering applications. The second example is a form of electronic paper. In both cases, it is the unique characteristics of TIR that make these practical devices possible. TIR is commonly said to occur when the angle of incidence exceeds the critical angle. Yet this notion is based on the inherent approximation of the ray model of light, an idea that is physically incorrect for any system of finite extent. Rather, the finite wavefront is equivalent to a superposition of a distribution of plane waves, which in turn have a range of propagation directions. Another fundamental shortcoming is that in any real system there is some degree of absorption loss in the materials. As a result, in reality, TIR is never truly total and the critical angle is never truly critical. Nevertheless, there is a profound quantitative difference between TIR and metallic reflection. In addition, in the case of TIR, the reflection can be modified by changing the external medium, which creates interesting possibilities. It is worth considering these ideas a bit more carefully and quantitatively. Light rays traveling from plastic (n1 = 1.5) to air (n2 = 1.0) will be transmitted through the interface for small angles of incidence, and the reflectance grows rapidly as a function of angle as the angle of incidence approaches the critical angle, (see Figure 1). It is important to note how tiny the angular range is in the plot in Figure 1. For all angles of incidence below the critical anFigure 1. The graph illustrates reflectance versus angle of incidence very close to the critical angle (indicated by the dotted vertical line).
Casting Single Crystal Silicon: Novel Defect Profiles from BP Solar's Mono<sup>2</sup><sup> TM </sup>Wafers (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Overcoming Resolution Attenuation During Tilted Cryo-EM Data Collection (2023)

Structural biology efforts using cryogenic electron microscopy are frequently stifled by specimens adopting "preferred orientations" on grids, leading to anisotropic map resolution and impeding structure determination. Tilting the specimen stage during data collection is a generalizable solution but has historically led to substantial resolution attenuation. Here, we develop updated data collection and image processing workflows and demonstrate, using multiple specimens, that resolution attenuation is negligible or significantly reduced across tilt angles. Reconstructions with and without the stage tilted as high as 60° are virtually indistinguishable. These strategies allowed the reconstruction to 3 Å resolution of a bacterial RNA polymerase with preferred orientation. Furthermore, we present a quantitative framework that allows cryo-EM practitioners to define an optimal tilt angle for dataset acquisition. These data reinforce the utility of employing stage tilt for data collection and provide quantitative metrics to obtain isotropic maps.
A Control Lyapunov Approach for Feedback Control of Cable-Suspended Robots (2007)

This paper considers a feedback control technique for cable suspended robots under input constraints, using control Lyapunov functions (CLF). The motivation for this work is to develop an explicit feedback control law for cable robots to asymptotically stabilize it to a goal point with positive input constraints. The main contributions of this paper are as follows: (i) proposal for a CLF candidate for a cable robot, (ii) a CLF based positive controllers for multiple inputs. An example of a three degrees-of-freedom cable suspended robot is presented to illustrate the proposed methods
Guest Editorial - Special issue on computational intelligence in telecommunications networks and internet services - Part II (2003)

S.429-431
Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2 (2017)

Polycomb repressive complex 2 (PRC2) is a key chromatin modifier responsible for methylation of lysine 27 in histone H3. PRC2 has been shown to interact with thousands of RNA species in vivo, but understanding the physiological function of RNA binding has been hampered by the lack of separation-of-function mutants. Here, we use comprehensive mutagenesis and hydrogen deuterium exchange mass spectrometry (HDX-MS) to identify critical residues for RNA interaction in PRC2 core complexes from <i>Homo sapiens</i> and <i>Chaetomium thermophilum</i>, for which crystal structures are known. Preferential binding of G-quadruplex RNA is conserved, surprisingly using different protein elements. Key RNA-binding residues are spread out along the surface of EZH2, with other subunits including EED also contributing, and missense mutations of some of these residues have been found in cancer patients. The unusual nature of this protein-RNA interaction provides a paradigm for other epigenetic modifiers that bind RNA without canonical RNA-binding motifs.
A 10-bit, 40-MS/s, 1.21 mW Pipelined SAR ADC Using Single-Ended 1.5-bit/cycle Conversion Technique (2011)

This paper presents an area efficient 10-bit, 40 MS/s SAR ADC. The design strategy to minimize the circuit area adopts the pipelined architecture. The 10-bit SAR ADC is divided into 4-bit (first stage) and 6-bit (second stage) SAR ADC. The two-stage pipelined structure achieves a reduction of the number of capacitors, which is the dominant source of the circuit area of SAR ADCs. To avoid the comparator offset issue, the proposed single-ended 1.5 bit/cycle algorithm is used in the first stage. The single-ended scheme reduces the conversion cycle while maintaining sufficient tolerance of the comparator offset. The second stage uses a pseudo C-2C architecture that is useful for minimizing the load capacitance of the residue amplifier and minimizing the circuit area. Fabricated in 65-nm CMOS with an active area of 0.06 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , it achieves a peak SNDR of 55.1 dB and a peak SFDR of 71.5 dB at 40 MS/s sampling rate. The power consumption is 1.21 mW.
ChemInform Abstract: Acid‐Promoted SN1/E1 Fragmentation/Dimerization of 2‐Cumylmalonates. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Multi-frequency heterodyne system for all-optical-technology-free ultrafast optical waveform measurement (2007)

A multi-frequency heterodyne system for ultrafast optical waveform measurement is demonstrated. Ultrafast waveform beyond photodiode bandwidth is downconverted to a slow-speed signal by photomixing with a locally generated ultra-flat comb. 80-GHz waveform was successfully measured. (2 pages)
Fluorine‐Enabled Cationic Gold Catalysis: Functionalized Hydration of Alkynes (2010)

Fluorine makes it possible: A cationic fluorine–gold species generated by fluorination of a low-valence gold complex mediates the “functionalized hydration” of alkynes. A triple bond is used to install a carbonyl group and two new bonds on the α-carbon atom, all occurring in one pot, under mild conditions and in very good yields (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
P4‐398: SurprisingHigh Resistance of Small all‐d‐Enantiomeric Peptides Against Metabolic Degradation and Modifications (2016)

Previously, we have developed all-D-enantiomeric peptides that are able to eliminate neurotoxic amyloid-beta peptide oligomers in vitro and show an improvement of cognition in various transgenic Alzheimer’s disease mice models in vivo. Such D-peptides are expected to be more stable against enzymatic proteolysis than their L-enantiomeric equivalents, and indeed, in vivo activity has been achieved in animals even after oral administration. In the current study we further examined the stability of our D-peptides in comparison to their corresponding L-peptides in vitro in simulated gastric and intestinal fluid as well as in plasma and liver microsomes. Simulated gastric and intestinal fluid was prepared according to the European Pharmacopoeia and the stability of the D- and L-peptides in these fluids was systematically examined for 24 hours. Additionally, the peptides’ stability was investigated in human plasma for 20 days and in human liver microsomes for 7 days. Potential degradation was followed by reversed-phase high-performance liquid chromatography (RP-HPLC). Notably, degradation was defined as any modification. Even deamidation of a side chain was detected and counted as degradation. The D-peptides showed surprisingly high stability in all investigated media in comparison to their L-enantiomeric equivalents. In simulated gastric and intestinal fluid the D-peptides remain stable (≥ 90%) within 24 hours. In contrast, the L-peptides were degraded by 25 to 70% in simulated gastric fluid within the same time period and were even completely metabolized within seconds in simulated intestinal fluid. In human plasma the L-peptides were metabolized more than 500 times faster than the D-peptides. And even in liver microsomes the D-peptides had a half-life that is more than 2000 times that of the L-peptides. Our study systematically reveals that our all-D-enantiomeric peptides are substantially more resistant against metabolism in the gastrointestinal tract, blood and liver than their L-enantiomeric equivalents. This surprisingly high stability allows oral administration of the drug candidate and may also explain the absence of adverse side effects even at high doses due to low levels of potential biologically active metabolites during treatment. In conclusion, all-D-enantiomeric peptides represent a promising new class of compounds for oral drug administration.
Molybdenum Tris(2,5-dimethylpyrrolide), a Rare Homoleptic Molybdenum(III) Monomer (2008)

The monomeric, homoleptic molybdenum(III) complex molybdenum tris(2,5-dimethylpyrrolide) has been prepared. Reduction with KC 8 in THF yields the molybdenum(II) complex potassium [molybdenum tris(2,5-dimethylpyrrolide)], while protonation with [H(OEt 2) 2][BAr (F) 4] yields a cationic species that contains an eta (1)-3 H-pyrrole ligand.
Molecular Dynamics Simulations. Molecular Dynamics Study on Shear Deformation of .BETA.-Silicon Nitride Single Crystal. (2000)

The deformation properties of β-silicon nitride under shear loading are investigated by molecular dynamics simulation using a three body empirical potential. Two cases of shear deformation, {1010} ‹0001› and {1010} ‹1210›, are analyzed, which are reported as the slip systems on the basis of experimental observation. The ideal shear strength of the β single crystal along these directions is somewhat smaller than the one of α-silicon nitride single crystal reported previously. Slip deformations take place in narrow bands, thickness of which are very thin. For the {1010} ‹0001› case, itis almost equal to the distance between the nearest neighbor atoms and for the {1010} ‹1210› case about 0.4nm.
Progress on the Multimirror Trap GOL-3 (2005)

Main results of researches on plasma heating and confinement of dense plasma in the multimirror trap GOL-3 are presented.Recently magnetic system of the facility was converted into completely multimirror one. This results in further improvement of energy confinement time of plasma with ion temperature ~1 keV. Collective plasma heating by ~120 kJ (~8 ɷs) relativistic electron beam results in Te ~ 2 keV at ~1021 m-3 density. High Te exists for ~10 μs. To this time Ti reaches ~2 keV. Ion temperature keeps at the high level during ~1 ms. The energy confinement time sufficiently increases and a value of nτE = (1.5 [divide] 3)·1018 m-3s.
Malfunction of Tenckhoff catheter due to a rare kink. (1989)

A case of sudden malfunction of Tenckhoff Catheter in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD) treatment is reported. Upon laparotomy, the catheter was found to form a knob inside the peritoneal cavity. The report emphasized on the simple but effective diagnostic value of abdominal X-ray and the importance of care of the bowel motion in a patient on CAPD.
A Hybrid-FPGA System for On-Board Data Processing Targeting the MATMOS FTIR Instrument (2008)

The MATMOS Fourier transform infrared (FTIR) spectrometer is one of three scientific instruments on the previously proposed MARVEL mission. MATMOS requires computationally intensive floating-point signal processing to reduce the amount of data prior to downlink. With the goal of reducing design time and the size and weight of instrument electronics, this paper presents an FTIR spectrometry implementation targeting the Xilinx Virtex-4FX hybrid-FPGA and its embedded PowerPC 405 processor. We explore different hardware and software optimizations and architectural configurations of the hybrid-FPGA system to demonstrate optimal performance in onboard data processing. By including a dedicated floating point unit and dot-product co-processor in the hardware as well as utilizing optimized single-precision math library functions and a modified IBM PowerPC performance library in the software, we demonstrate a more than 8x reduction in execution time compared to the non-optimized software only implementation. A dual-processor design concept as an enhancement that would further reduce the execution time is also presented.
A Sub-1 GHz Wireless Sensor Network Concentrator Using Multicollectors with Load Balancing for Improved Capacity and Performance (2021)

The exponential growth of IoT end devices creates the necessity for cost-effective solutions to further increase the capacity of IEEE802.15.4g-based wireless sensor networks (WSNs). For this reason, the authors present a wireless sensor network concentrator (WSNC) that integrates multiple collocated collectors, each of them hosting an independent WSN on a unique frequency channel. A load balancing algorithm is implemented at the WSNC to uniformly distribute the number of aggregated sensor nodes across the available collectors. The WSNC is implemented using a BeagleBone board acting as the Network Concentrator (NC) whereas collectors and sensor nodes realizing the WSNs are built using the TI CC13X0 LaunchPads. The system is assessed using a testbed consisting of one NC with up to four collocated collectors and fifty sensor nodes. The performance evaluation is carried out under race conditions in the WSNs to emulate high dense networks with different network sizes and channel gaps. The experimental results show that the multicollector system with load balancing proportionally scales the capacity of the network, increases the packet delivery ratio, and reduces the energy consumption of the IoT end devices.
Supplementary Figure 3 from Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity (2023)

&lt;p&gt;Cabozantinib-mediated granulocytic infiltration within tumors.&lt;/p&gt;
LUD01–014: Phase 1/2 study of chimeric monoclonal antibody cG250 in combination with vinblastine in patients with advanced renal cell carcinoma (ARCC) (2004)

2531 Background: To asses the safety and efficacy of the combination of cG250 and vinblastine in patients (pts) with ARCC. Methods: Eighteen pts with ARCC of clear cell histology and measurable disease were included. Pts received intravenous doses of cG250, 10 mg/m2, and vinblastine, 5 mg/m2, weekly for 8 weeks (wks) followed by a 2-wk rest period (one cycle). Pts were evaluated for toxicity and the development of human antichimeric antibody (HACA) prior to each treatment, and for response after each cycle. Treatment was continued unless pts had disease progression or limiting toxicity. Results: All pts were evaluable for toxicity and 16/18 for response. Pts characteristics were: gender (male-10, female-8); median age 63 (48–84); median Karnofsky performance status 90%. Nine pts received 1 cycle; 7/18 pts received ≥2 and 4/18 ≥3 cycles. WHO III/IV toxicities were anemia and neutropenia in 2/18 pts (11%) and 5/18 pts (28%), respectively. Other toxicities included WHO I/II fatigue in 6/18 pts (33%) and I/II neuropathy in 2/18 pts (11%). Of 18 pts, 4 pts are still on study and 14 have withdrawn (9 for PD during the 1st cycle, 3 for PD diagnosed after the 2nd cycle, and 2 at their own discretion). HACA were not developed. SD was observed in 7/16 (44%), and PD in 9 evaluable pts (56%). In 3 pts SD lasted 12+, 12.8+, and 17.8 months. For assessable pts followed longer than 12 months (10 pts), the 1-year progression free survival (PFS) rate was 30%. Median survival has not been reached yet. Conclusions: cG250 in combination with vinblastine is feasible and safe. A high rate of SD with prolonged PFS was observed that warrants further confirmation in a randomized phase II trial. No significant financial relationships to disclose.
Production of Cyclic Tetrasaccharide with 6‐α‐Glucosyltransferase and α‐Isomaltosyltransferase (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Dual-wavelength efficient two-photon photorelease of glycine by π-extended dipolar coumarins (2019)

Photolabile protecting groups (PPGs) releasing bioactive compounds upon two-photon excitation have emerged as increasingly popular tools to control and study physiological processes. Yet the limited two-photon photosensitivity of many cages is still a critical issue for applications. We herein report the design, synthesis and photophysical study of polarized extended coumarinyl derivatives which show large two-photon sensitivity (up to 440 GM) at two complementary wavelengths in the NIR spectral range. DFT calculations demonstrate that subtle tuning of polarization in the ground-state and confinement of the photo-induced intramolecular charge transfer upon excitation is responsible for enhancing two-photon absorption while maintaining large uncaging efficiency. These findings open a new engineering route towards efficient coumarinyl PPGs.
Preoperative and Postoperative Sagittal Plane Hip Kinematics in Patients with Femoroacetabular Impingement during Level Walking (2011)

The results supported the hypothesis that surgical intervention for FAI restores more normal patterns of gait and provides objective support that the surgical procedure is useful. The results help establish motion capture as a potential method for quantitatively assessing the outcome in FAI surgical interventions. The presence of abnormal reversals in hip flexion has been reported in end-stage hip osteoarthritis, and the presence of these reversals in FAI patients reinforces the idea of FAI being a precursor to hip osteoarthritis.