gebhart/patrepeval huggingface dataset:
A Singular System with Precise Dosing and Spatiotemporal Control of CRISPR‐Cas9 (2019)

Several genome engineering applications of CRISPR-Cas9, an RNA-guided DNA endonuclease, require precision control of Cas9 activity over dosage, timing, and targeted site in an organism. While some control of Cas9 activity over dose and time have been achieved using small molecules, and spatial control using light, no singular system with control over all the three attributes exists. Furthermore, the reported small-molecule systems lack wide dynamic range, have background activity in the absence of the small-molecule controller, and are not biologically inert, while the optogenetic systems require prolonged exposure to high-intensity light. We previously reported a small-molecule-controlled Cas9 system with some dosage and temporal control. By photocaging this Cas9 activator to render it biologically inert and photoactivatable, and employing next-generation protein engineering approaches, we have built a system with a wide dynamic range, low background, and fast photoactivation using a low-intensity light while rendering the small-molecule activator biologically inert. We anticipate these precision controls will propel the development of practical applications of Cas9.
Synaptic transistors based on a tyrosine-rich peptide for neuromorphic computing (2021)

In this article, we propose an artificial synaptic device based on a proton-conducting peptide material. By using the redox-active property of tyrosine, the Tyr-Tyr-Ala-Cys-Ala-Tyr-Tyr peptide film was utilized as a gate insulator that shows synaptic plasticity owing to the formation of proton electric double layers. The ion gating effects on the transfer characteristics and temporal current responses are shown. Further, timing-dependent responses, including paired-pulse facilitation, synaptic potentiation, and transition from short-term plasticity to long-term plasticity, have been demonstrated for the electrical emulation of biological synapses in the human brain. Herein, we provide a novel material platform that is bio-inspired and biocompatible for use in brain-mimetic electronic devices.
Bridge-And-Roll Demonstration in GRIPhoN (Globally Reconfigurable Intelligent Photonic Network) (2010)

We describe a ROADM architecture for a dynamically reconfigurable photonic network and demonstrate the performance of a photonic-layer bridge-and-roll that could improve the operational flexibility of optical transport networks.
Epithelial cell transforming 2 is regulated by Yes-associated protein 1 and mediates pancreatic cancer progression and metastasis (2021)

Pancreatic ductal adenocarcinoma (PDAC) is highly metastatic and represents one of the deadliest forms of human cancers. Previous studies showed that activation of Yes-associated protein 1 (YAP1) plays a key role in malignant transformation in the pancreas. In this study, we found that YAP1 regulates the expression of epithelial cell transforming 2 (ECT2), a guanine nucleotide exchange factor for Rho-like GTPases. By immunohistochemistry analysis of human tissues, we show that ECT2 is highly expressed in primary PDAC and liver metastasis but not in normal pancreas. These correlations were also observed in a mouse model of PDAC, where pancreatic transformation is driven by mutants of <i>Kras</i> and <i>Trp53</i>. Notably, nuclear ECT2 is upregulated in the transition from preneoplastic lesions to PDAC. High levels of YAP1 or ECT2 expression correlates with the poor overall survival rate of patients with PDAC. We further demonstrate that ECT2 is required for pancreatic cancer cell proliferation and migration in vitro. Finally, using a syngeneic orthotopic xenograft mouse model for pancreatic cancer, we found that ablation of ECT2 expression reduces pancreatic cancer growth and dissemination to the liver. These findings highlight the critical role of ECT2 in promoting pancreatic cancer growth and metastasis and provides insights into the development of novel methods for early detection and treatment.<b>NEW & NOTEWORTHY</b> Pancreatic ductal adenocarcinoma is one of the deadliest forms of human cancers. In this study, we identified a novel signaling mechanism involved in PDAC progression and metastasis. Yes-associated protein 1 mediates the expression of epithelial cell transforming 2, which is elevated in PDAC and correlates with poor survival. Epithelial cell transforming 2 is required for PDAC growth and metastasis. This study provides insights into the development of novel methods for early detection and treatment of PDAC.
“PERFECT”: An Entirely New Methodology for Synthesizing Perfluorinated Compounds (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Corporate feed design for microstrip arrays (1993)

A design technique for an embedded microstrip corporate feed is presented. The aim of the design is to shape each corporate feed junction to achieve a tapered and in-phase output current distribution. From this, a Dolph-Chebyshev array sum pattern may be constructed. In the experiments, the designed corporate feed is used to excite a five-element equispaced linear array of overlay microstrip dipoles. It is found both theoretically and experimentally that a 20-dB Dolph-Chebyshev broadside sum pattern can be synthesized in the H-plane at 8.5 GHz. Mutual coupling among the dipoles is included in this analysis. The pattern degradation due to manufacturing tolerances on the alignment between the feed network and the dipole array is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Quantification of External Limiting Membrane Disruption Caused by Diabetic Macular Edema from SD-OCT (2012)

In this preliminary study, we were able to show that automated quantification of ELM disruption is feasible and can differentiate continuous ELM in normal subjects from disrupted ELM in subjects with CSME. We have started determining the relationships of quantitative ELM disruption markers to visual outcome in patients undergoing treatment for CSME.
Two-Layer Scaffold Platforms for Drug Screening of Nasopharyngeal Epithelial Cells (2020)

A two-layer scaffold platform was designed for drug screening without using fluorescence staining to examine the effectiveness of the tested compounds. Nasopharyngeal epithelial (NP460) cells were used in this work. Typically, NP460 cells could not squeeze into the 10 μm narrow trenches but preferred to migrate on the top ridges. However, NP460 cells could migrate into 10 μm wide trenches after being stimulated by transforming growth factor beta-1 ( TGF-β1) as the cells became more active. This double-layer scaffold platform served as a drug screening device by tracking the number of cells migrated into narrow trenches after drug treatment to test and monitor the effectiveness of a compound in a biomimetic microenvironment.
High-throughput Fabrication of Plasmonic Nanoantenna Arrays Using Nanostencils for Spectroscopy and Biosensing (2011)

We demonstrate a novel approach for high-throughput and high-resolution fabrication of engineered infrared plasmonic antenna arrays with reusable nanostencils for vibrational spectroscopy. Optical responses of these antennas are identical to ones fabricated by electron-beam lithography.
Successive crosstalk cancellation facing the dynamic situation in very-high-speed digital subscriber line 2 systems (2011)

Broadband digital transmission over cable wires, such as in very-high-speed digital subscriber line 2 systems, applies the discrete multitone technique in combination with a bit-loading procedure. The crosstalk interference among the different cables inside a binder is the major performance degradation in the systems. Different crosstalk cancellation schemes considering computation complexity as well as the quality-of-service (QoS) aspect have been investigated to improve the system performance. Nowadays, driven by the newest high-layer applications the QoS requirements are more critical and a dynamic situation happening quite often in reality has to be considered. In this situation, new active cable lines might significantly influence the existing running lines in terms of achieved data rates. Therefore a successive crosstalk cancellation scheme is presented in this study to deal with the dynamic situation. The performance degradation because of the new active lines is predicted. Based on the prediction a line-independent partial cancellation with successive procedure is performed until the QoS requirements are fulfilled again.
CD4+ T-cell lines used to evaluate a Mycobacterium avium subsp. paratuberculosis (MAP) peptide vaccine (2015)

The aim of the study was to establish a protocol for generation of MAP-specific T-cell lines and to use these lines for evaluation of a peptide vaccine. A protocol for culturing T-cell lines from peripheral blood of goats naturally infected with MAP was established. CD4+ T cells were positively selected using an anti CD4 mAb and Dynabeads. Sorted CD4+ cells were cultivated with purified protein derivative from MAP (PPDj) or E. coli sonicate, IL-2, and IL-15. After two cultivation cycles, T cells were tested for recall responses in a proliferative T-cell assay. T-cell line responses were in average 92 % for PPDj, and -3 % for E. coli sonicate. CD4+ T-cell lines stimulated with PPDj showed a 6 fold increase in IFN- γ production compared to controls. These results indicated that the T-cell lines were MAP-specific. The protocol was subsequently used to evaluate MAP-specific peptides as vaccine antigens. T-cell lines were now generated by cultivating CD4+ cells with peptides instead of PPDj. Initially, both healthy and MAP-infected goats were vaccinated with 119 peptides defined by in silico analysis. Cellular responses to the peptides were not detected using standard IFN- γ plasma ELISA. However, testing of T-cell lines from the MAP-infected goats identified peptides that induced strong proliferative responses. The 23 peptides inducing the strongest responses were used in a second vaccination trail with healthy goat kids. Vaccinated kids developed strong IFN-γ and antibody responses, and these MAP-specific peptides show great potential for use in a subunit vaccine. Generation of T-cell lines was a valuable tool for selecting MAP vaccine antigens, and the protocol can also be applied for identifying vaccine candidates for other diseases.
Writers and Readers of Histone Acetylation: Structure, Mechanism, and Inhibition (2014)

Histone acetylation marks are written by histone acetyltransferases (HATs) and read by bromodomains (BrDs), and less commonly by other protein modules. These proteins regulate many transcription-mediated biological processes, and their aberrant activities are correlated with several human diseases. Consequently, small molecule HAT and BrD inhibitors with therapeutic potential have been developed. Structural and biochemical studies of HATs and BrDs have revealed that HATs fall into distinct subfamilies containing a structurally related core for cofactor binding, but divergent flanking regions for substrate-specific binding, catalysis, and autoregulation. BrDs adopt a conserved left-handed four-helix bundle to recognize acetyllysine; divergent loop residues contribute to substrate-specific acetyllysine recognition.
Mucociliary Transport Deficiency in Syrian Hamsters with SARS-CoV-2 (2021)

RATIONALE: SARS-CoV-2 causes COVID-19 disease and infects respiratory epithelial cells, but how it affects ciliated cell function and the mucociliary transport apparatus is unknown. Abnormal mucociliary function could predispose to COVID-19 progression and/or secondary infection. Micro-optical coherence tomography (μOCT) is a novel method to simultaneously visualize and quantify the functional microanatomy of airways. Here, we established a hamster model of COVID-19 and evaluated their tracheas by μOCT. METHODS: Adult golden Syrian hamsters were inoculated intranasally with 3.2 × 105 (high dose, HD, N=4) or 3.2 × 104 (low dose, LD, N=4) plaque-forming units of SARS-CoV-2 (WA/1 strain). Clinical signs were monitored daily, nasal brushes collected intermittently, and hamsters were euthanized seven days (D7) after inoculation. Tracheas were imaged by μOCT, nasal washes and bronchial alveolar lavage fluid (BALF) from right lung lobes were collected for quantitation of viral load by qRT-PCR, and left lungs were inflated with and fixed in 10% neutral buffered formalin for histological analysis. Age-matched hamsters were used as uninfected controls (N=5). RESULTS: SARS-CoV-2 hamsters lost weight through D7 in dose-dependent fashion (-11% in HD vs. -4% in LD, p=0.02) and HD hamsters showed moderate lethargy. Nasal brushes on D4 and nasal washes on D7 contain 105-106 genome copies of virus while BALF on D7 was less than 104 genome copies and intermittently detected in LD. Histology demonstrated patchy and multifocal interstitial pneumonia (type II pneumocyte hyperplasia and mononuclear cell infiltrate), with ∼20% area affected in HD that was more variable in LD. Functional microanatomy of tracheas revealed diminished area of active ciliary beating (control 18 ± 2 vs. LD 7 ± 1%, p=0.0002, control vs. HD 9 ± 1%, p=0.001), reduced ciliary beat frequency (control 10.88 ± 0.70 vs. LD 8.83 ± 0.34 Hz, p=0.01, control vs. HD 8.26 ± 0.33 Hz, p=0.001), and decreased periciliary liquid depth (control 6.41 ± 0.18 vs. HD 5.61± 0.12 μ m, p=0.027). Mucociliary transport rate was diminished (control 0.84 ± 0.19 vs. LD 0.48 ± 0.16 vs. HD 0.37 ± 0.13 mm/min) although not statistically significant. Additional cohorts are in progress. CONCLUSION: SARS-Cov-2 infected hamsters exhibit reduced body weight, high viral load, and histopathological injury through 7 days. SARS-CoV-2 caused functional deficits of the mucociliary transport apparatus, consistent with early findings in COVID-19 patients (see Vijaykumar et al.). Abnormal ciliated cell function is important to SARS-CoV-2 pathogenesis, and may help monitor progression and represent a treatment opportunity for COVID-19.
Design considerations for short-wavelength operation of 790-nm-pumped Tm-doped fibers (2009)

Tm-doped 790-nm-pumped silica fiber lasers are excellent candidates for producing emission at <1.95 microm, but achieving efficient operation at these wavelengths requires careful attention to fiber design because of the characteristic three-level reabsorption effects. We present a discussion of methods for mitigation of these effects and two high-efficiency systems that are capable of producing up to 70 W at <1.92 microm.
A Chemically Competent Thiosulfuranyl Radical on the Escherichia coli Class III Ribonucleotide Reductase (2014)

The class III ribonucleotide reductases (RNRs) are glycyl radical (G•) enzymes that provide the balanced pool of deoxynucleotides required for DNA synthesis and repair in many facultative and obligate anaerobic bacteria and archaea. Unlike the class I and II RNRs, where reducing equivalents for the reaction are delivered by a redoxin (thioredoxin, glutaredoxin, or NrdH) via a pair of conserved active site cysteines, the class III RNRs examined to date use formate as the reductant. Here, we report that reaction of the Escherichia coli class III RNR with CTP (substrate) and ATP (allosteric effector) in the absence of formate leads to loss of the G• concomitant with stoichiometric formation of a new radical species and a "trapped" cytidine derivative that can break down to cytosine. Addition of formate to the new species results in recovery of 80% of the G• and reduction of the cytidine derivative, proposed to be 3'-keto-deoxycytidine, to dCTP and a small amount of cytosine. The structure of the new radical has been identified by 9.5 and 140 GHz EPR spectroscopy on isotopically labeled varieties of the protein to be a thiosulfuranyl radical [RSSR2]•, composed of a cysteine thiyl radical stabilized by an interaction with a methionine residue. The presence of a stable radical species on the reaction pathway rationalizes the previously reported [(3)H]-(k(cat)/K(M)) isotope effect of 2.3 with [(3)H]-formate, requiring formate to exchange between the active site and solution during nucleotide reduction. Analogies with the disulfide anion radical proposed to provide the reducing equivalent to the 3'-keto-deoxycytidine intermediate by the class I and II RNRs provide further evidence for the involvement of thiyl radicals in the reductive half-reaction catalyzed by all RNRs.
Quantifying and Recommending Expertise When New Skills Emerge (2013)

In the rapidly changing technological world of today, new technical areas emerge quickly, and new skills related to them garner high demand. In this paper, our goal is to recommend experts for new skills and skill topics. We propose multiple predictive models to utilize data from different enterprise sources: employee assessment data, free-text skill description data, and employee tags from corporate social media. These models include collaborative filtering, content-based, and novel hybrid recommendation approaches. We apply them in an empirical study of real-world corporate data, in which we compare and contrast the models to gain insight on the drivers of performance. The considered data is both structured and unstructured, messy, subjective, and incomplete. The central theme of the paper is to understand how to use data from different sources and what each data source contributes in the expertise management domain.
BackLink: Supervised Local Training with Backward Links (2022)

Empowered by the backpropagation (BP) algorithm, deep neural networks have dominated the race in solving various cognitive tasks. The restricted training pattern in the standard BP requires end-to-end error propagation, causing large memory cost and prohibiting model parallelization. Existing local training methods aim to resolve the training obstacle by completely cutting off the backward path between modules and isolating their gradients to reduce memory cost and accelerate the training process. These methods prevent errors from flowing between modules and hence information exchange, resulting in inferior performance. This work proposes a novel local training algorithm, BackLink, which introduces inter-module backward dependency and allows errors to flow between modules. The algorithm facilitates information to flow backward along with the network. To preserve the computational advantage of local training, BackLink restricts the error propagation length within the module. Extensive experiments performed in various deep convolutional neural networks demonstrate that our method consistently improves the classification performance of local training algorithms over other methods. For example, in ResNet32 with 16 local modules, our method surpasses the conventional greedy local training method by 4.00\% and a recent work by 1.83\% in accuracy on CIFAR10, respectively. Analysis of computational costs reveals that small overheads are incurred in GPU memory costs and runtime on multiple GPUs. Our method can lead up to a 79\% reduction in memory cost and 52\% in simulation runtime in ResNet110 compared to the standard BP. Therefore, our method could create new opportunities for improving training algorithms towards better efficiency and biological plausibility.
Relating balance and conditional independence in graphical models (2022)

When data are available for all nodes of a Gaussian graphical model, then, it is possible to use sample correlations and partial correlations to test to what extent the conditional independencies that encode the structure of the model are indeed verified by the data. In this paper, we give a heuristic rule useful in such a validation process: When the correlation subgraph involved in a conditional independence is balanced (i.e., all its cycles have an even number of negative edges), then a partial correlation is usually a contraction of the corresponding correlation, which often leads to conditional independence. In particular, the contraction rule can be made rigorous if we look at concentration subgraphs rather than correlation subgraphs. The rule is applied to real data for elementary gene regulatory motifs.
Time dependent threshold-voltage fluctuations in NAND flash memories: From basic physics to impact on array operation (2015)

Introduction: Random telegraph noise (RTN) during read and charge detrapping during data retention cause time dependent threshold voltage (VT) fluctuations in NAND flash memories [1-9]. This paper reviews and discusses the physics of these phenomena and the impact on NAND array reliability based on characteristics of aggressively scaled 2D planar NAND cells [10][11]. The discussion is further extended to 3D NAND.
Microréacteurs pour l'industrie (2008)

Les microréacteurs ouvrent des possibilités nouvelles pour les industries. Ils s'inscrivent dans une démarche de qualité, de sécurité, de créativité et d'intensification des procédés. À ce titre, ils constituent une des briques de l'usine du futur. Transformations chimiques ou physiques y sont mises en œuvre. Les phénomènes et principes de base sont décrits, ainsi que certaines initiatives industrielles, tout en pointant les limites d'application de ces technologies innovantes.
Supplemental table 2 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies (2023)

&lt;p&gt;Anti-proliferative activity of MS417 across cancer cell lines&lt;/p&gt;
Supplemental Figure Legends from EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer (2023)

&lt;p&gt;Legends for Supplemental Figures S1-S6&lt;/p&gt;
Dynamically adapting mechanism for translation lookaside buffer shootdowns (2023)

An operating system (OS) of a processing system having a plurality of processor cores determines a cost associated with different mechanisms for performing a translation lookaside buffer (TLB) shootdown in response to, for example, a virtual address being remapped to a new physical address, and selects a TLB shootdown mechanism to purge outdated or invalid address translations from the TLB based on the determined cost. In some embodiments, the OS selects an inter-processor interrupt (IPI) as the TLB shootdown mechanism if the cost associated with sending an IPI is less than a threshold cost. In some embodiments, the OS compares the cost of using an IPI as the TLB shootdown mechanism versus the cost of sending a hardware broadcast to all processor cores of the processing system as the shootdown mechanism and selects the shootdown mechanism having the lower cost.
Titelbild: Efficiency and Fidelity in a Click‐Chemistry Route to Triazole Dendrimers by the Copper(I)‐Catalyzed Ligation of Azides and Alkynes (Angew. Chem. 30/2004) (2004)

Strukturelle Diversität ist bei Dendrimersynthesen möglich, die auf dem hoch effizienten Aufbau von Triazolen aus funktionalisierten Aziden und Alkinen beruhen. In ihrer Zuschrift auf S. 4018 ff. beschreiben V. V. Fokin et al. die Anwendung dieser Cu I ‐katalysierten Umwandlung, die bis zur dritten und vierten Dendrimergeneration nahezu quantitativ verläuft.
Theoretical Study of an Effective Field Plate Termination for SiC Devices Based on High-k Dielectrics (2006)

A classical implementation of the field plate technique is the oxide ramp termination. This paper presents improvements of the breakdown voltage for both SiC JBDs and SBDs, obtained by using high-k dielectrics. A study regarding the influence of the dielectric permittivity and thickness on the off-state performances of the diodes is included. It is shown that Si3N4 is to be preferred to SiO2 for the dielectric ramp. Termination efficiencies up to 96% are reported.