gebhart/patrepeval huggingface dataset:
A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells (2005)

Many key regulatory proteins, including members of the Ras family of GTPases, are modified at their C terminus by a process termed prenylation. This processing is initiated by the addition of an isoprenoid lipid, and the proteins are further modified by a proteolytic event and methylation of the C-terminal prenylcysteine. Although the biological consequences of prenylation have been characterized extensively, the contributions of prenylcysteine methylation to the functions of the modified proteins are not well understood. This reaction is catalyzed by the enzyme isoprenylcysteine carboxyl methyltransferase (Icmt). Recent genetic disruption studies have provided strong evidence that blocking Icmt activity has profound consequences on oncogenic transformation. Here, we report the identification of a selective small-molecule inhibitor of Icmt, 2-[5-(3-methylphenyl)-1-octyl-1H-indol-3-yl]acetamide (cysmethynil). Cysmethynil treatment results in inhibition of cell growth in an Icmt-dependent fashion, demonstrating mechanism-based activity of the compound. Treatment of cancer cells with cysmethynil results in mislocalization of Ras and impaired epidermal growth factor signaling. In a human colon cancer cell line, cysmethynil treatment blocks anchorage-independent growth, and this effect is reversed by overexpression of Icmt. These findings provide a compelling rationale for development of Icmt inhibitors as another approach to anticancer drug development.
Structured illumination for the extension of imaging interferometric microscopy (2008)

Structured illumination applied to imaging interferometric microscopy (IIM) allows extension of the resolution limit of low numerical aperture objective lenses to ultimate linear systems limits (<approximately lambda/4 in air) without requiring a reference beam around the objective lens. Instead, the reference beam is provided by an illumination beam just at the edge of the optical system numerical aperture resulting in a shift of the recorded spatial frequencies (equivalent to an intermediate frequency). The restoration procedure is discussed. This technique is adaptable readily to existing microscopes, since extensive access to the imaging system pupil plane is not required.
Tailoring Nanostructure Morphology for Enhanced Targeting of Dendritic Cells in Atherosclerosis (2016)

Atherosclerosis, a leading cause of heart disease, results from chronic vascular inflammation that is driven by diverse immune cell populations. Nanomaterials may function as powerful platforms for diagnostic imaging and controlled delivery of therapeutics to inflammatory cells in atherosclerosis, but efficacy is limited by nonspecific uptake by cells of the mononuclear phagocytes system (MPS). MPS cells located in the liver, spleen, blood, lymph nodes, and kidney remove from circulation the vast majority of intravenously administered nanomaterials regardless of surface functionalization or conjugation of targeting ligands. Here, we report that nanostructure morphology alone can be engineered for selective uptake by dendritic cells (DCs), which are critical mediators of atherosclerotic inflammation. Employing near-infrared fluorescence imaging and flow cytometry as a multimodal approach, we compared organ and cellular level biodistributions of micelles, vesicles (i.e., polymersomes), and filomicelles, all assembled from poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) block copolymers with identical surface chemistries. While micelles and filomicelles were respectively found to associate with liver macrophages and blood-resident phagocytes, polymersomes were exceptionally efficient at targeting splenic DCs (up to 85% of plasmacytoid DCs) and demonstrated significantly lower uptake by other cells of the MPS. In a mouse model of atherosclerosis, polymersomes demonstrated superior specificity for DCs (p < 0.005) in atherosclerotic lesions. Furthermore, significant differences in polymersome cellular biodistributions were observed in atherosclerotic compared to naïve mice, including impaired targeting of phagocytes in lymph nodes. These results present avenues for immunotherapies in cardiovascular disease and demonstrate that nanostructure morphology can be tailored to enhance targeting specificity.
A Multiplex Fragment-Ion-Based Method for Accurate Proteome Quantification (2019)

Multiplex proteome quantification with high accuracy is urgently required to achieve a comprehensive understanding of dynamic cellular and physiological processes. Among the existing quantification strategies, fragment-ion-based methods can provide highly accurate results, but the multiplex capacity is limited to 3-plex. Herein, we developed a multiplex pseudo-isobaric dimethyl labeling (m-pIDL) method to extend the capacity of the fragment-ion-based method to 6-plex by one-step dimethyl labeling with several millidalton and dalton mass differences between precursor ions and enlarging the isolation window of precursor ions to 10 m/ z during data acquisition. m-pIDL showed high quantification accuracy within the 20-fold dynamic range. Notably, the ratio compression was 1.13-fold in a benchmark two-proteome model (5:1 mixed E. coli proteins with HeLa proteins as interference), indicating that by m-pIDL, the ratio distortion of isobaric labeling approaches and the approximate 40% ratio shift of the label-free quantification strategy could be effectively eliminated. Additionally, m-pIDL did not show ratio variation among post-translational modifications (CV = 6.66%), which could benefit the measurement of universal protein properties for proteomic atlases. We further employed m-pIDL to monitor the time-resolved responses of the TGF-β-induced epithelial-mesenchymal transition (EMT) in lung adenocarcinoma A549 cell lines, which facilitated the finding of new potential regulatory proteins. Therefore, the 6-plex quantification of m-pIDL with the remarkably high accuracy might create new prospects for comprehensive proteome analysis.
Computational Design of Lignin Depolymerization Catalysts (2012)

Lignin is a major component of plant cell walls that is typically underutilized in selective conversion strategies for renewable fuels and chemicals. The mechanisms by which thermal and catalytic treatments deconstruct lignin remain elusive, for which quantum mechanical calculations can offer fundamental insights. In this work, a computational approach has been used to elucidate the reductive deconstruction pathway of a ruthenium-catalyzed system. Transition states have been computed to determine the rate-limiting steps for a catalyst that cleaves arylether linkages. Our calculations are supported by experimental synthesis and kinetic and thermodynamic measurements of the deconstruction of model lignin dimers by a ruthenium catalyst with the ultimate objective of designing new catalysts to eventually utilize lignin in biorefineries.
Hyperspectral imaging in highly scattering media by the spectral phasor approach using two filters (2018)

Hyperspectral imaging is a common technique in fluorescence microscopy to obtain the emission spectrum at each pixel of an image. However, methods to obtain spectral resolution based on diffraction gratings or integrated prisms work poorly when the sample is strongly scattering. We developed a microscope named the DIVER that collects the fluorescence emission over a very large angle. Since the fluorescence light after passing through the multiple scattering sample is not collimated, the use of grating or prisms strongly limits the amount of light that can be used with available hyperspectral devices. Here we show that 2 filters that accept uncollimated light over a large aperture are sufficient to calculate the spectral phasor rather than displaying the entire spectrum. Using the properties of the spectral phasors, we can resolve spectral components and perform the type of data analyses that are usually performed in hyperspectral image analysis.
High Q, precision SC cut resonators with low acceleration sensitivity (2003)

A new mounting structure has enabled the construction of high Q resonators with very low acceleration sensitivity. Values in the range of mid parts in 10/sup 11/ to low parts in 10/sup 10/ per g have been achieved with a simple planar support structure. Utilizing a thin chemically etched lead-frame, a four-point mount with built in stress relief has been designed to mount in the plane of the resonator. The advantages of this structure include good symmetry, minimal residual manufacturing stresses, and minimal asymmetric vibratory stresses. Many different configurations have been designed and built using 8 and 10 mm 10 MHz 3/sup rd/ overtone SC cut plano-convex crystals with excellent results.
A Novel HLA-A2–restricted CTL Epitope of Tumor-associated Antigen L6 can Inhibit Tumor Growth In Vivo (2012)

Vaccines utilizing cytotoxic T lymphocyte (CTL) epitopes are promising for the treatment of cancer and chronic infectious diseases. Tumor-associated antigen L6 (TAL6) is overexpressed in some epithelial cancer cells. In this report, we detected TAL6 expression in breast cancer tissue using quantitative reverse-transcriptase-polymerase chain reaction. We found that >80% of breast tumor tissue highly expressed TAL6 compared with adjacent normal breast tissue. To identify CTL epitopes from TAL6, we synthesized 18 peptides for HLA-A2-binding assay based on the MHC-binding motif using 4 computer prediction programs. Positive binders identified by ELISA were immunized in HLA-A2 transgenic (A2 Tg) mice. Two peptides, peptide 2 and peptide 5, induced T-cell responses in A2 Tg mice. To confirm whether these peptides could be processed and presented to induce T-cell responses in vivo, A2 Tg mice were immunized with plasmid DNA encoding TAL6. We found that both peptides 2 and 5 stimulated splenocytes from TAL6-immunized mice to secrete interferon-γ. However, only peptide 5 could induce expression of the cytolytic molecule CD107a on CD8+ T cells after immunization. Furthermore, peptide 5-immunized A2 Tg mice could inhibit the growth of TAL6-positive tumors (EL4/TAL6/HLA-A2) in A2 Tg mice but not in wild-type mice. These results demonstrate that the TAL6-derived CTL epitope could induce HLA-A2-restricted immunity against TAL6-expressing tumor cells.
The FDA-Approved Anti-Asthma Medicine Ciclesonide Inhibits Lung Cancer Stem Cells through Hedgehog Signaling-Mediated SOX2 Regulation (2020)

Ciclesonide is an FDA-approved glucocorticoid (GC) used to treat asthma and allergic rhinitis. However, its effects on cancer and cancer stem cells (CSCs) are unknown. Our study focuses on investigating the inhibitory effect of ciclesonide on lung cancer and CSCs and its underlying mechanism. In this study, we showed that ciclesonide inhibits the proliferation of lung cancer cells and the growth of CSCs. Similar glucocorticoids, such as dexamethasone and prednisone, do not inhibit CSC formation. We show that ciclesonide is important for CSC formation through the Hedgehog signaling pathway. Ciclesonide reduces the protein levels of GL1, GL2, and Smoothened (SMO), and a small interfering RNA (siRNA) targeting SMO inhibits tumorsphere formation. Additionally, ciclesonide reduces the transcript and protein levels of SOX2, and an siRNA targeting SOX2 inhibits tumorsphere formation. To regulate breast CSC formation, ciclesonide regulates GL1, GL2, SMO, and SOX2. Our results unveil a novel mechanism involving Hedgehog signaling and SOX2 regulated by ciclesonide in lung CSCs, and also open up the possibility of targeting Hedgehog signaling and SOX2 to prevent lung CSC formation.
<title>Design of compact camera zoom lenses with high zoom ratios</title> (1997)

The process behind compact cameras, capable of achieving high zoom ratios are described. In addition to the development of a suitable new type of zoom lens, the internal focusing is essential to the design. The study focuses upon current major lens types, especially a three-group zoom lens which are composed of positive, positive and negative refractive powers for respective lens groups. First, requirements on the development of zoom lenses are described. Then properties of lens types are discussed. Using similar specifications, applications of standard zoom lenses providing higher aperture are shown. The characteristics of these zoom lenses are then summarized.
Electrodeposition of amorphous Ni-Cr-P alloys (1988)

The impact of increasing LNR was strongly related to survival, especially in patients with no macroscopic peritoneal disease. Stratification of this subpopulation of node positive EOC based on nodal burden provides a significant prognostic value that may be considered in future staging and aid in management decisions.
Automatic Optimize-time Validation for Binary Optimizers (2022)

We propose an approach called automatic optimize-time validation for binary optimizers. Our approach does not involve executing the whole program for validation but selecting a small part of code (1 to 100 instructions) for the target test code. It executes the target code and its optimized code with several input data during binary optimization. One benefit is that we can test a small part of an actual customer's code during binary optimization. Our approach can be used to test several input data not included in the target code, which is the most beneficial aspect of the approach. If the results are the same after execution, we will use the optimized code for the final output code. If the results differ, we can consider a couple of option, e.g., while developing a binary optimizer, we can abort the compilation with an error message to easily detect a bug. After a binary optimizer becomes generally available, we can use the input code for the final output code to maintain compatibility. Our goal is for the output binary code to be compatible, fast, and small. We focused on how to improve compatibility in this study. We implemented our approach in our binary optimizer and successfully detected one new bug. We used a very small binary program to observe the worst case of increased compilation time and output binary file size. Our implementation showed that our approach increases optimization time by only 0.02% and output binary file size by 8%.
Inside Front Cover: A Combinatorial Library of Photocrosslinkable and Degradable Materials (Adv. Mater. 19/2006) (2006)

Abstract The first combinatorial library of degradable photocrosslinked materials is reported on p. 2614 by Anderson, Burdick, and co‐workers. The inside cover shows a three‐dimensional representation of the generic macromer, superimposed onto a microarray of materials. It is believed that this library approach will allow for the rapid screening and design of degradable polymers for a variety of applications.
An Improved Relay Selection Scheme with Hybrid Relaying Protocols (2007)

In this paper, we propose an improved relay selection scheme based on a hybrid relaying protocol (RS-HRP). In the proposed scheme, all the relays are included into two groups, referred to as an amplify and forward (AAF) and a decode and forward (DAF) relay groups. The relays which decode successfully are included in the DAF group and the rest of relays, which fail to decode correctly, are included in the AAF group. The best relay, which maximizes the destination SNR, will be selected from all relays in both AAF and DAF relay groups. If it is selected from the AAF group, it will amplify the received signal while if it is selected from the DAF group, it will decode the received signals and re-encode. Results show that the proposed relay selection scheme significantly outperforms the conventional AAF selection scheme and this performance gain considerably grows as the number of relays increases. It also approaches the perfect DAF relay selection as the SNR increases.
Red-shifted click beetle luciferase mutant expands the multicolor bioluminescent palette for deep tissue imaging (2020)

For <i>in vivo</i> multicolor bioluminescence applications, red and near-infrared signals are desirable over shorter wavelength signals because they are not as susceptible to light attenuation by blood and tissue. Herein, we describe the development of a new click beetle luciferase mutant, CBG2, with a red-shifted color emission. When paired with NH<sub>2</sub>-NpLH2 luciferin, CBG2 (λ = 660 nm) and CBR2 (λ = 730 nm) luciferases can be used for simultaneous dual-color bioluminescence imaging in deep tissue. Using a spectral unmixing algorithm tool it is possible to distinguish each spectral contribution. Ultimately, this enzyme pair can expand the near-infrared bioluminescent toolbox to enable rapid visualization of multiple biological processes in deep tissue using a single substrate.
Coupling loss minimization of slow light slotted photonic crystal waveguides using mode matching with continuous group index perturbation (2012)

We experimentally demonstrate highly efficient coupling into a slow light slotted photonic crystal waveguide. With optical mode converters and group index tapers that provide good optical mode matching and impedance matching, a nearly flat transmission over the entire guided mode spectrum of 68.8 nm range with 2.4 dB minimum insertion loss is demonstrated. Measurements also show up to 20 dB baseline enhancement and 30 dB enhancement in the slow light region, indicating that it is possible to design highly efficient and compact devices that benefit from the slow light enhancement without increasing the coupling loss.
Construction and Characterization of a Nonproliferative El Tor Cholera Vaccine Candidate Derived from Strain 638 (2000)

In recent clinical assays, our cholera vaccine candidate strain, Vibrio cholerae 638 El Tor Ogawa, was well tolerated and immunogenic in Cuban volunteers. In this work we describe the construction of 638T, a thymidine auxotrophic version of improved environmental biosafety. In so doing, the thyA gene from V. cholerae was cloned, sequenced, mutated in vitro, and used to replace the wild-type allele. Except for its dependence on thymidine for growth in minimal medium, 638T is essentially indistinguishable from 638 in the rate of growth and morphology in complete medium. The two strains showed equivalent phenotypes with regard to motility, expression of the celA marker, colonization capacity in the infant mouse cholera model, and immunogenicity in the adult rabbit cholera model. However, the ability of this new strain to survive environmental starvation was limited with respect to that of 638. Taken together, these results suggest that this live, attenuated, but nonproliferative strain is a new, promising cholera vaccine candidate.
Diversity Routing to Improve Delay-Jitter Tradeoff in Uncertain Network Environments (2019)

In this paper we propose a novel approach to deliver better delay-jitter performance in dynamic networks. Dynamic networks experience rapid and unpredictable fluctuations and hence, a certain amount of uncertainty about the delay-performance of various network elements is unavoidable. This uncertainty makes it difficult for network operators to guarantee a certain quality of service (in terms of delay and jitter) to users. The uncertainty about the state of the network is often overlooked to simplify problem formulation, but we capture it by modeling the delay on various links as general and potentially correlated random processes. Within this framework, a user will request a certain delay-jitter performance guarantee from the network. After verifying the feasibility of the request, the network will respond to the user by specifying a set of routes as well as the proportion of traffic which should be sent through each one to achieve the desired quality of service. We propose to use mean-variance analysis as the basis for traffic distribution and route selection, and show that this technique can significantly reduce the end-to-end jitter because it accounts for the correlated nature of delay across different paths. The resulting traffic distribution is often non-uniform and the fractional flow on each path is the solution to a simple convex optimization problem. We conclude the paper by commenting on the potential application of this method to general transportation networks.
An insulin epidermal growth factor-binding protein from Drosophila has insulin-degrading activity. (1989)

We have recently described the purification and characterization of an insulin-degrading enzyme (IDE) from Drosophila melanogaster that can cleave porcine insulin, is highly conserved through evolution and is developmentally regulated. We now report that the IDE is, in fact, an insulin EGF-binding protein (dp100) that we had isolated previously from Drosophila using an antihuman EGF receptor antiserum. This conclusion is based upon the following evidence. (a) dp100, identified by its ability to cross-link to labeled insulin, EGF, and transforming growth factor-alpha (TGF-alpha), and to be immunoprecipitated by anti-EGF receptor antisera, copurifies with the IDE activity. Thus, the purified IDE can be affinity labeled with either 125I-insulin, 125I-EGF, or 125I-TGF-alpha, and this labeling is specifically inhibited with unlabeled insulin, EGF, and the insulin B chain. (b) The antiserum to the human EGF receptor, which recognizes dp100, is able to specifically immunoprecipitate the insulin-degrading activity. (c) The purified IDE preparation contains a single protein of 110 kD which is recognized by both the anti-EGF receptor antiserum and anti-Drosophila IDE antiserum. (d) Polyclonal antiserum to the purified IDE, which specifically recognized only the 110-kD band in Drosophila Kc cells, immunoprecipitates dp100 cross-linked to 125I-TGF-alpha and dp100 cross-linked to 125I-insulin from the purified IDE preparation. (e) EGF, which competes with insulin for binding to dp100, also inhibits the degradation of insulin by the purified IDE. These results raise the possibility that a functional interaction between the insulin and EGF growth factor families can occur which is mediated by the insulin-degrading enzyme.
A Low-Complexity Endurance Modulation for Flash Memory (2021)

The repeated program/erase (P/E) cycles wear out flash memory cells which limits the device’s lifetime. The larger the injected/erased charge, the faster the wear out rate and thus there is interest in reducing the percentage of cells programmed to high voltage levels. Conventional data shaping techniques often introduce a nonnegligible overhead as well as incurring additional complexity to encode the input data into shaped codewords and decode the read data. We propose a novel lossless yet simple endurance modulation technique that relies solely on the error-correction code (ECC) to retrieve the original data. This idea is motivated by the fact that ECCs are usually designed to correct channel errors towards the end of the device’s lifetime and hence at early age, the ECC can be jointly used for channel error correction and endurance demodulation. The proposed scheme consists of data shaping by flipping bits in a controlled manner and simple max-log demodulation to recover those flipped bits. The simulation results show that the proposed scheme does not undermine the device’s ability to recover the original data if the shaping gain is adjusted as the device ages. Once the channel errors exceed a prescribed threshold, the controller disables the endurance modulation and operates in normal mode.
A New Peroxide Fragmentation: Efficient Chemical Generation of <sup>1</sup>O<sub>2</sub> in Organic Media (2009)

Monoactivated derivatives of 1,1-dihydroperoxides undergo an unprecedented base-promoted fragmentation to efficiently generate singlet oxygen (1O2) in anhydrous organic solvents.