gebhart/patrepeval huggingface dataset:
Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells (2023)

The incorporation of light-responsive domains into engineered proteins has enabled control of protein localization, interactions, and function with light. We integrated optogenetic control into proximity labeling (PL), a cornerstone technique for high-resolution proteomic mapping of organelles and interactomes in living cells. Through structure-guided screening and directed evolution, we installed the light-sensitive LOV domain into the PL enzyme TurboID to rapidly and reversibly control its labeling activity with low-power blue light. "LOV-Turbo" works in multiple contexts and dramatically reduces background in biotin-rich environments such as neurons. We used LOV-Turbo for pulse-chase labeling to discover proteins that traffick between endoplasmic reticulum, nuclear, and mitochondrial compartments under cellular stress. We also showed that instead of external light, LOV-Turbo can be activated by BRET from luciferase, enabling interaction-dependent PL. Overall, LOV-Turbo increases the spatial and temporal precision of PL, expanding the scope of experimental questions that can be addressed with PL.
Functional Calcitonin Gene-related Peptide Receptors Are Formed by the Asymmetric Assembly of a Calcitonin Receptor-like Receptor Homo-oligomer and a Monomer of Receptor Activity-modifying Protein-1 (2007)

In addition to their interactions with hetero-trimeric G proteins, seven-transmembrane domain receptors are now known to form multimeric complexes that can include receptor homo- or hetero-oligomers and/or accessory proteins that modulate their activity. The calcitonin gene-related peptide (CGRP) receptor requires the assembly of the seven-transmembrane domain calcitonin receptor-like receptor with the single-transmembrane domain receptor activity-modifying protein-1 to reach the cell surface and be active. However, the relative stoichiometric arrangement of these two proteins within a receptor complex remains unknown. Despite recent advances in the development of protein-protein interactions assays, determining the composition and stoichiometric arrangements of such signaling complexes in living cells remains a challenging task. In the present study, we combined bimolecular fluorescence complementation (BiFC) with bioluminescence resonance energy transfer (BRET) to probe the stoichiometric arrangement of the CGRP receptor complex. Together with BRET competition assays, co-immunoprecipitation experiments, and BiFC imaging, dual BRET/BiFC revealed that functional CGRP receptors result from the association of a homo-oligomer of the calcitonin receptor-like receptor with a monomer of the accessory protein receptor activity-modifying protein-1. In addition to revealing the existence of an unexpected asymmetric oligomeric organization for a G protein-coupled receptor, our study illustrates the usefulness of dual BRET/BiFC as a powerful tool for analyzing constitutive and dynamically regulated multiprotein complexes.
Endovascular Treatment of Visceral Artery Aneurysms (2007)

Visceral artery aneurysms, although uncommon, can present with life-threatening hemorrhage. The increasing use of imaging studies has allowed for earlier identification and intervention of these aneurysms, thus avoiding the high morbidity and mortality associated with rupture. The treatment options for visceral artery aneurysms range from conventional open surgical repair to minimally invasive techniques using covered stents or embolization materials. Anatomic features and patient selection determine which treatment option would result in the most durable treatment and outcome. This article reviews our experience with the endovascular treatment of visceral artery aneurysms.
Integrated bake/chill system for across-wafer temperature uniformity control in photoresist processing (2009)

An integrated bake/chill thermal processing module is developed and experimentally evaluated to achieve spatial temperature uniformity of a silicon wafer throughout the entire processing temperature cycle of ramp, hold, and quench in lithography. The module uses a set of thermoelectric devices which are used to provide distributed heating and cooling to the substrate for uniformity and transient temperature control. The experimental results demonstrate that the wafer spatial temperature uniformity is within ±0.3 and ±0.1°C during transient and steady-state thermal processing, respectively.
Entwicklung struktureller Template zur Mikrotubulihemmung durch weitgehende Abwandlung der Epothilon‐Grundstruktur (2005)

Ein Mikrotubulistabilisator (1) wurde durch starke Modifizierung (Kreise im Bild) der natürlichen Epothilon-Grundstruktur erhalten. Trotz deutlich unterschiedlicher Struktur ist die biologische Aktivität von 1 vergleichbar mit der von Epothilon A oder Taxol! Die Entdeckung von 1 zeigt, wie die starke Modifizierung von Naturstoffen zu neuen strukturellen Templaten für die Hemmung von Mikrotubuli und damit vielleicht zu neuen Wirkstoffen führen kann.
Membrane separation systems---A research and development needs assessment (1990)

Industrial separation processes consume a significant portion of the energy used in the United States. A 1986 survey by the Office of Industrial Programs estimated that about 4.2 quads of energy are expended annually on distillation, drying and evaporation operations. This survey also concluded that over 0.8 quads of energy could be saved in the chemical, petroleum and food industries alone if these industries adopted membrane separation systems more widely. Membrane separation systems offer significant advantages over existing separation processes. In addition to consuming less energy than conventional processes, membrane systems are compact and modular, enabling easy retrofit to existing industrial processes. The present study was commissioned by the Department of Energy, Office of Program Analysis, to identify and prioritize membrane research needs in light of DOE's mission. Each report will be individually cataloged.
Effects of Cell Seeding and Cyclic Stretch on the Fiber Remodeling in an Extracellular Matrix–Derived Bioscaffold (2008)

The porcine small intestine submucosa, an extracellular matrix-derived bioscaffold (ECM-SIS), has been successfully used to enhance the healing of ligaments and tendons. Since the collagen fibers of ECM-SIS have an orientation of +/- 30 degrees , its application in improving the healing of the parallel-fibered ligament and tendon may not be optimal. Therefore, the objective was to improve the collagen fiber alignment of ECM-SIS in vitro with fibroblast seeding and cyclic stretch. The hypothesis was that with the synergistic effects of cell seeding and mechanical stimuli, the collagen fibers in the ECM-SIS can be remodeled and aligned, making it an improved bioscaffold with enhanced conductive properties. Three experimental groups were established: group I (n = 14), ECM-SIS was seeded with fibroblasts and cyclically stretched; group II (n = 13), ECM-SIS was seeded with fibroblasts but not cyclically stretched; and group III (n = 8), ECM-SIS was not seeded with fibroblasts but cyclically stretched. After 5 days' experiments, the scaffolds from all the three groups (n = 9 for group I; n = 8 for groups II and III) were processed for quantification of the collagen fiber orientation with a small-angle light scattering (SALS) system. For groups I and II, in which the scaffolds were seeded with fibroblasts, the cell morphology and orientation and newly produced collagen fibrils were examined with confocal fluorescent microscopy (n = 3/group) and transmission electronic microscopy (n = 2/group). The results revealed that the collagen fiber orientation in group I was more aligned closer to the stretching direction when compared to the other two groups. The mean angle decreased from 25.3 degrees to 7.1 degrees (p < 0.05), and the associated angular dispersion was also reduced (37.4 degrees vs. 18.5 degrees , p < 0.05). In contrast, groups II and III demonstrated minimal changes. The cells in group I were more aligned in the stretching direction than those in group II. Newly produced collagen fibrils could be observed along the cells in both groups I and II. This study demonstrated that a combination of fibroblast seeding and cyclic stretch could remodel and align the collagen fiber orientation in ECM-SIS bioscaffolds. The better-aligned ECM-SIS has the prospect of eliciting improved effects on enhancing the healing of ligaments and tendons.
Reproductive Cytotoxicity Is Predicted by Magnetic Resonance Microscopy and Confirmed by Ubiquitin–Proteasome Immunohistochemistry in a Theophylline-Induced Model of Rat Testicular and Epididymal Toxicity (2005)

This study investigated the testicular changes in the rat induced by the nonspecific phosphodiesterase inhibitor, theophylline using magnetic resonance microscopy (MRM) and ubiquitin immunostaining techniques. In vivo T1- and T2-weighted images were acquired at 2 T under anesthesia. Increased signal observed in the theophylline-treated rats suggests that leakage of MRM contrast was occurring. In vivo MRM results indicate that day 16 testis displayed an increased T1-weighted water signal in the area of the seminiferous tubule that decreased by day 32. These findings were validated by histopathology, suggesting that in vivo MRM has the sensitivity to predict changes in testis and epididymal tissues. The participation of the ubiquitin system was investigated, using probes for various markers of the ubiquitin-proteasome pathway. MRM can be used to detect subtle changes in the vascular perfusion of organ systems, and the up-regulation/mobilization of ubiquitin-proteasome pathway may be one of the mechanisms used in theophylline-treated epididymis to remove damaged cells before storage in the cauda epididymis. The combined use of in vivo MRM and subsequent tissue or seminal analysis for the presence of ubiquitin in longitudinal studies may become an important biomarker for assessing testis toxicities drug studies.
Don’t Take the Premise for Granted: Mitigating Artifacts in Natural Language Inference (2019)

Natural Language Inference (NLI) datasets often contain hypothesis-only biases-artifacts that allow models to achieve non-trivial performance without learning whether a premise entails a hypothesis. We propose two probabilistic methods to build models that are more robust to such biases and better transfer across datasets. In contrast to standard approaches to NLI, our methods predict the probability of a premise given a hypothesis and NLI label, discouraging models from ignoring the premise. We evaluate our methods on synthetic and existing NLI datasets by training on datasets containing biases and testing on datasets containing no (or different) hypothesis-only biases. Our results indicate that these methods can make NLI models more robust to dataset-specific artifacts, transferring better than a baseline architecture in 9 out of 12 NLI datasets. Additionally, we provide an extensive analysis of the interplay of our methods with known biases in NLI datasets, as well as the effects of encouraging models to ignore biases and fine-tuning on target datasets. 1
Prognostic value of ERG oncoprotein in prostate cancer recurrence and cause‐specific mortality (2013)

While the presence of ERG expression at the time of surgery was not predictive of earlier relapse or PCSM, the relative intensity and composite score for ERG expression was prognostic for the development of biochemical relapse, metastases, and PCSM. Quantitative ERG scoring may be useful to identify patients who would benefit from adjuvant treatment or closer follow-up, allowing more accurate individual patient treatment plans.
Concentrated Colloids of Silica-Encapsulated Gold Nanoparticles: Colloidal Stability, Cytotoxicity, and X-ray Absorption (2007)

As an effort to develop a new, effective, nontoxic X-ray contrast agent, the concentrated colloids of silica-encapsulated gold nanoparticles (Au@SiO2 NPs) were fabricated and their colloidal stability, cytotoxicity, and X-ray absorption were investigated. The concentrated colloidal NPs were manufactured by forming a 4 nm-thick silica shell on the surface of each Au NP with 15 nm diameter, followed by enrichment to [Au] = 100 mM. They were very stable in water: the NPs were well separated each other without forming agglomerates and their optical property was very similar to that before enrichment. The colloidal stability of the NPs in biological environment was strongly dependent on their previous morphology in water. The NPs with minor shell damage were stable in phosphate buffered saline (PBS) solution: both in water and in PBS solution, they showed very similar morphology and optical property. However, the NPs with profound shell damage formed big agglomerates in PBS solution, resulting in the red-shift and broadening of the Au surface plasmon resonance peak. Cell viability and proliferation assessments revealed the biocompatibility of the Au@SiO2 NPs: no apparent cytotoxicity was observed even at 100 ppm NPs. The concentrated colloidal NPs showed very strong X-ray absorption. Their relative X-ray transmittance to water was comparable to that of a commercial agent. Considering these, the concentrated colloids of the Au@SiO2 NPs are suitable for an X-ray contrast agent.
New use for an old drug: COX‐independent anti‐inflammatory effects of sulindac in models of cystic fibrosis (2016)

Overall, sulindac decrease lung inflammation by a mechanism independent of cycolooxygenase. This drug could be beneficially employed in CF.
Comparison of ultraviolet APDs grown on free-standing GaN and sapphire substrates (2010)

There is a need for semiconductor-based ultraviolet photodetectors to support avalanche gain in order to realize better performance andmore effective compete with existing technologies. Wide bandgap III-Nitride semiconductors are the promising material system for the development of avalanche photodiodes (APDs) that could be a viable alternative to current bulky UV detectors such as photomultiplier tubes. In this paper, we review the current state-of-the-art in IIINitride visible-blind APDs, and present our latest results on GaN APDs grown on both conventional sapphire and low dislocation density free-standing c- and m-plane GaN substrates. Leakage current, gain, and single photon detection efficiency (SPDE) of these APDs were compared. The spectral response and Geiger-mode photon counting performance of UV APDs are studied under low photon fluxes, with single photon detection capabilities as much as 30% being demonstrated in smaller devices. Geiger-mode operation conditions are optimized for enhanced SPDE.
A spheroid model for the sound radiation of a loudspeaker on a sound bar (2017)

The sound radiation of a loudspeaker on a sound bar with a slender shape is analyzed. Measurements and boundary element method (BEM) simulations of a rectangular rigid enclosure with a flat piston turn out to be in close agreement up to the frequency limit imposed by the discretization chosen for the BEM. Looking up for a shorter computation time, we consider an analytic model based on a geometrical approximation of the sound bar by a prolate spheroid. The corresponding spheroidal coordinate system allows for an analytical solution of the sound-radiation problem. The following parameters are adjusted: geometry of the ellipse-based spheroid, size and location of the circular piston, minimum order of the spheroidal wave functions that ensures convergence. In the light of the BEM results, we also predict the frequency validity of the analytic model. In order to improve the control of the acoustical field radiated by a sound bar, we discuss the influence of the enclosure edges on the regularity of the sound field pattern. [Work supported by the ANR-13-CORD-0008 EDISON 3D grant from the French National Agency of Research.]
Automatic Diachronic Normalization of Polish Texts (2018)

The paper presents a method for the automatic diachronic normalization of Polish texts – the procedure, which, for a given historical text, returns its contemporary spelling. The method applies finite-state transducers, defined in a sublanguage of the Thrax formalism. The paper discusses linguistic issues, such as evolution in spelling of the Polish language, as well as implementation aspects, such as efficiency or testing the proposed method.
Whittler (1983)

69 WHITTLER Say you are angry at your Hands and you cut them off. You make of the green olive-wood New hands with claws for fingers. They will sprout blossoms then, Knuckles, thumbs hiding under bloom. Say you are angry again, you will Carve wooden flowers for your hands. The bees will come there then Confused by your skill, thirsting. Say you are angry, and whittle The little bees, buttons on your stumps. Honey will begin to drip bright And sticky down the skin to your elbows. Say then life is in your hands. The one thing you cannot outlive. J.B. GOODENOUGH ...
Neutrophilia of infection/inflammation: are we really dealing with "inflamed" leukocytes? (1998)

We adopted whole blood flow cytometry and direct labeling of the CD11b/CD18 and CD62L antigens to study the relationship between their expression and leukocytosis in patients with infection/inflammation, acute stress and healthy volunteers. Mean +/- S.D. channel fluorescence intensity of CD11b/CD18 antigen on peripheral blood polymorphonuclears did not differ between patients with infection/ inflammation (173+/-78) and controls (167+/-72), but was significantly (p = 0.04) reduced in stress (135+/-60). No correlation was found between CD11b/CD18 antigen level and either polymorphonuclears absolute number or serum C-reactive protein. A significant negative correlation was noted between CD62L antigen expression on polymorphonuclears and their absolute number. We assume that cells with increased CD11b/CD18 surface concentrations are retained in the capillaries and that part of the leukocytes in the peripheral blood are stressed leukocytes with reduced CD11b/CD18. Thus, leukocytes detected in peripheral blood are not necessarily the most "inflamed" ones.
Ruthenium Polypyridyl Complexes Containing a Conjugated Ligand LDQ (LDQ = 1-[4-(4′-methyl)-2,2′-bipyridyl]-2-[4-(4′-N,N′-tetramethylene-2,2′-bipyridinum)]ethene): Synthesis, Characterization, and Photoinduced Electron Transfer at Solution−Zeolite Interfaces (2009)

Photoinduced electron transfer from sensitizers attached to zeolite surface to electron acceptors within the zeolite provides opportunities for long-lived charge separation, as well as potential utilization of the charge separated species. In this study, the focus is on the ruthenium polypyridyl compound [(bpy)2RuLDQ]4+ (where bpy = bipyridine, and LDQ = 1-[4-(4′-methyl)-2,2′-bipyridyl]-2-[4-(4′-N,N′-tetramethylene-2,2′-bipyridinium)]ethene) and its unquaternized analogue of structural formula [(bpy)2RuL]2+ (L = trans-1,2-bis[4-(4′-methyl)-2,2′-bipyridyl]ethene). Both complexes show strong metal-to-ligand charge-transfer (MLCT) and olefinic ligand based absorption bands. The emission of [(bpy)2RuLDQ]4+ in solution is quenched, whereas the [(bpy)2RuL]2+ complex exhibits emission at 675 nm. The quenching is attributed to the intramolecular electron transfer from the Ru center to the diquat (DQ) moiety upon photoexcitation. The [(bpy)2RuLDQ]4+ complex is stable upon visible light illumination, while [(bpy)2RuL]2+ is photochemically unstable. Nanocrystalline zeolite Y with particle size of ∼80 nm was prepared and characterized by diffraction and electron microscopy. Protonated [(bpy)2RuL]2+ and [(bpy)2RuLDQ]4+ were attached to the surface of the zeolite Y by ion-exchange and permanent incorporation into the supercage, respectively. The zeolite-encapsulated [(bpy)2RuLDQ]4+ species was found to be emissive at 695 nm with at lifetime of 796 ns. Intermolecular electron transfer from photoexcited [(bpy)2RuLDQ]4+ to methylviologen (MV2+) in solution was not observed. However, in the zeolite, ∼40% of the initial MV+• generated via photoinduced electron transfer from surface-bound [(bpy)2RuLLQ]4+ survived for the duration of the experiment (milliseconds). The long-lived viologen radical resulted from a competitive effect between the back electron transfer from MV+• to Ru3+ (kb = 3.0 × 105 s−1) with a self-exchange electron propagation between the densely packed viologens (khop = 2.0 × 105 s−1) that moves the charge away from the surface of the zeolite.
Finding Patterns in a Knowledge Base using Keywords to Compose Table Answers (2014)

We aim to provide table answers to keyword queries against knowledge bases. For queries referring to multiple entities, like "Washington cities population" and "Mel Gibson movies", it is better to represent each relevant answer as a table which aggregates a set of entities or entity-joins within the same table scheme or pattern. In this paper, we study how to find highly relevant patterns in a knowledge base for user-given keyword queries to compose table answers. A knowledge base can be modeled as a directed graph called knowledge graph, where nodes represent entities in the knowledge base and edges represent the relationships among them. Each node/edge is labeled with type and text. A pattern is an aggregation of subtrees which contain all keywords in the texts and have the same structure and types on node/edges. We propose efficient algorithms to find patterns that are relevant to the query for a class of scoring functions. We show the hardness of the problem in theory, and propose path-based indexes that are affordable in memory. Two query-processing algorithms are proposed: one is fast in practice for small queries (with small patterns as answers) by utilizing the indexes; and the other one is better in theory, with running time linear in the sizes of indexes and answers, which can handle large queries better. We also conduct extensive experimental study to compare our approaches with a naive adaption of known techniques.
Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs (2019)

These results suggest a paradigm by which targeted drugs may have unexpected off-target effects in heterogeneous cell populations <i>in vivo</i> via control of a physical platform for receipt of extracellular ligands.
A reconfigurable distributed all-digital clock generator core with SSC and skew correction in 22nm high-k tri-gate LP CMOS (2012)

Diverse spread spectrum clocking (SSC) generation requirements necessitate multiple reference clocks, extra pins, and off-chip components. With analog integer-n PLL-based clock generators, it is difficult to meet all these needs with a common reference clock. One disadvantage is that the frequency resolution in an integer-n PLL is limited by the reference frequency. A lower reference frequency limits the bandwidth and lock time, amplifies jitter from the reference, and increases the loop filter area. Additionally, analog PLLs suffer from unpredictable loop dynamics and clock skews with PVT, mismatch, and transistor leakage, further exacerbated by process scaling. Turning off and waking up an analog PLL requires charging or discharging loop filter capacitors which is inherently slow. This paper presents an all-digital clock generation architecture which (1) provides fractional-n capability in the digital domain; (2) implements SSC within the PLL loop; (3) performs digital clock deskew; and (4) provides dynamic loop bandwidth adjustment to shorten lock time.
High-power Source of THz Radiation based on Orientation-patterned GaAs pumped by a Fiber Laser (2006)

We demonstrate a µW-level, 100-MHz repetition rate THz source based on parametric down-conversion in orientation-patterned GaAs pumped by a femtosecond all-fiber laser at 2 µm. The demonstrated source should be suitable for imaging and spectroscopy.