gebhart/patrepeval huggingface dataset:
A Simple and Affordable Method to Create Nonsense Mutation Clones of p53 for Studying the Premature Termination Codon Readthrough Activity of PTC124 (2023)

(1) Background: A premature termination codon (PTC) can be induced by a type of point mutation known as a nonsense mutation, which occurs within the coding region. Approximately 3.8% of human cancer patients have nonsense mutations of p53. However, the non-aminoglycoside drug PTC124 has shown potential to promote PTC readthrough and rescue full-length proteins. The COSMIC database contains 201 types of p53 nonsense mutations in cancers. We built a simple and affordable method to create different nonsense mutation clones of p53 for the study of the PTC readthrough activity of PTC124. (2) Methods: A modified inverse PCR-based site-directed mutagenesis method was used to clone the four nonsense mutations of p53, including W91X, S94X, R306X, and R342X. Each clone was transfected into p53 null H1299 cells and then treated with 50 μM of PTC124. (3) Results: PTC124 induced p53 re-expression in H1299-R306X and H1299-R342X clones but not in H1299-W91X and H1299-S94X clones. (4) Conclusions: Our data showed that PTC124 more effectively rescued the C-terminal of p53 nonsense mutations than the N-terminal of p53 nonsense mutations. We introduced a fast and low-cost site-directed mutagenesis method to clone the different nonsense mutations of p53 for drug screening.
Poly(trimethylene carbonate) as an elastic biodegradable film for human embryonic stem cell-derived retinal pigment epithelial cells (2017)

Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great promise for these RPE cell therapies. The aim of the present study was to assess whether a flexible, elastic and biodegradable poly(trimethylene carbonate) (PTMC) film promotes the formation of functional hESC-RPE and performs better than often used biodegradable poly(d,l-lactide) (PDLLA) film. Human ESC-RPE maturation and functionality on PTMC films was assessed by cell proliferation assays, RPE-specific gene and protein expression, phagocytic activity and growth factor secretion. It is demonstrated that the mechanical properties of PTMC films have close resemblance to those of the native Bruch's membrane and support the formation hESC-RPE monolayer in serum-free culture conditions with high degree of functionality. In contrast, use of PDLLA films did not lead to the formation of confluent monolayers of hESC-RPE cells and had unsuitable mechanical properties for retinal application. In conclusion, the present study indicates that flexible and elastic biodegradable PTMC films show potential for retinal tissue engineering applications. Copyright © 2017 John Wiley & Sons, Ltd.
Development of cVSSI-APCI for the Improvement of Ion Suppression and Matrix Effects in Complex Mixtures (2022)

The new ionization technique termed vibrating sharp-edge spray ionization (cVSSI) has been coupled with corona discharge to investigate atmospheric pressure chemical ionization (APCI) capabilities. The optimized source was evaluated for its ability to enhance ion signal intensity, overcome matrix effects, and limit ion suppression. The results have been compared with state-of-the-art ESI source performance as well as a new APCI-like source. In methanol, the ion signal intensity increased 10-fold and >10-fold for cocaine and the suppressed analytes, respectively. The ability to overcome ion suppression was improved from 2-fold to 16-fold for theophylline and vitamin D2, respectively. For aqueous samples, ion signal levels increased by two orders of magnitude for all analytes. In both solvent systems, the signal-to-noise ratios also increased for all suppressed analytes. One example of the characterization of low-ionizing (by ESI or cVSSI alone) species in the presence of high-ionizing species by direct analysis from a cotton swab is presented. The work is discussed with respect to the advantages of cVSSI-APCI for direct, in situ, and field analyses.
Limits of Visibly Transparent Luminescent Solar Concentrators (2017)

Visibly transparent solar harvesting surfaces are an exciting new approach to harvesting solar energy around buildings and mobile electronics to improve their efficiency and autonomy without impacting their appearance. The recent demonstration of ultraviolet (UV) and near‐infrared (NIR) selective light harvesters have enabled transparent luminescent solar concentrators (LSCs) that boast unparalleled scalability, flexibility, aesthetic quality, and affordability. Consequently, the question of the efficiency limits has emerged in these new systems. In this perspective, the theoretical efficiency limits of these concentrator systems are reviewed and practical considerations are outlined to approach these limits. For UV and UV/NIR selective harvesting single‐junction transparent LSCs are constrained thermodynamically to 21%, which increases to over 35% in fully transparent multipanel devices with light trapping. In deriving these limits, key material and engineering challenges are identified to fully optimize transparent solar concentrators that can push them towards commercial reality.
Adaptation and Evaluation of the Output-Deviations Metric to Target Small-Delay Defects in Industrial Circuits (2010)

Timing-related defects are a major cause of test escapes and field returns for very deep-submicron (VDSM) integrated circuits. Small-delay variations induced by crosstalk, process variations, power supply noise, and resistive opens and shorts can cause timing failures in a design, leading to quality and reliability concerns. This article describes the authors' work with a previously proposed test-grading technique that uses output deviations for screening small-delay defects.
Oligosaccharide Heterogeneity of Insulin Receptors. Comparison of N-Linked Glycosylation of Insulin Receptors in Adipocytes and Brain* (1986)

We tested the hypothesis that the molecular weight discrepancy between insulin receptors in brain and adipocytes is due to differences in glycosylation by treating photoaffinity-labeled insulin receptors from both tissues with endo-beta-N-acetylglucosaminidase F (Endo F) and analyzing the products by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Endo F removed glycans from the adipocyte 125-kilodalton (kDa) subunit and the brain 115-kDa subunit in a manner dependent upon the concentration of enzyme and time of incubation. At a maximally effective concentration of Endo F, the adipocyte alpha-subunit was reduced from 125-kDa to 100-kDa and the brain alpha-subunit from 115-kDa to 100-kDa. We also examined the type of oligosaccharides present in both alpha-subunits by treating the proteins with endo-beta-N-acetylglucosaminidase H (Endo H), which selectively removes high mannose residues, and neuraminidase. Endo H treatment reduced the apparent molecular weight of both the adipocyte and brain alpha-subunits. In both receptors, the deglycosylated product obtained with Endo H was larger than that generated by Endo F. The adipocyte alpha-subunit demonstrated a shift in mobility on sodium dodecyl sulfate gels after neuraminidase treatment, whereas the brain alpha-subunit did not. We conclude from these studies that 1) The discrepancy in apparent molecular weight of alpha-subunits in brain and adipocytes is due to differences in N-linked glycosylation; 2) high mannose and complex type oligosaccharides are present in both receptor types; and 3) the complex oligosaccharides in the adipocyte alpha-subunit are terminated in a manner different from the complex glycans of the brain alpha-subunit.
Finite size effects and rotational relaxation in superfluid helium nanodroplets: Microwave-infrared double-resonance spectroscopy of cyanoacetylene (2000)

Microwave-infrared double-resonance spectroscopy has been used to probe the solvation environment and its influence on the rotational relaxation of a cyanoacetylene molecule embedded in a superfluid He4 nanodroplet. The results support a model in which (within any given rotational state) the guest molecules are distributed over a set of spectroscopically inequivalent states which are most likely “particle-in-a-box” states originating from the confinement of the guest molecule within the droplet. Revisitation of previously collected microwave–microwave double-resonance data suggests that transitions between these states occur at a rate which is comparable to the rotational relaxation rate, but not fast enough as to produce motionally narrowed, homogeneous absorption lines. The relative intensities of the rotational lines in the microwave-infrared double-resonance spectra are observed to depend strongly on the average droplet size. In the large droplet limit we can explain the observed pattern by invoking a “strong collision” regime, i.e., one in which the branching ratios of the rotational relaxation do not depend on the initial rotational state. For small droplets we speculate that, because of finite size effects, the density of (surface) states may become discontinuous, producing deviations from the “thermal” behavior of the larger systems.
Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses (2018)

Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV) <i>in vivo</i> Here we utilized <i>ex vivo</i> global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response. Dendritic cells that were deficient in IL-1 receptor signaling showed dysregulation of cell-intrinsic defense genes and loss of viral control during WNV infection. Surprisingly, we found that in wild-type cells, IL-1β treatment, in the absence of infection, drove the transcription of IFN-β and ISGs at late times following treatment. Expression of these antiviral innate immune genes was dependent on the transcription factor IFN regulatory factor 3 (IRF3) and appears to reflect a general shift in IL-1β signaling from an early inflammatory response to a late IFN-mediated response. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection in myeloid cells through a process of IL-1β-to-IRF3 signaling crosstalk. Strategies to exploit these cytokines in the activation of host defense programs should be investigated as novel therapeutic approaches against individual pathogens.<b>IMPORTANCE</b> West Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses.
Design optimization for high-speed per-address two-level branch predictors (1997)

Per-address two-level branch predictors have been shown to be among the best predictors and have been implemented in current microprocessors. However, as the cycle time of modern microprocessors continues to decrease, the implementation of set-associative per-address two-level branch predictors will become more difficult. Instead, direct-mapped designs may be more attractive. In this paper, we investigate an alternative implementation of the per-address two-level predictor referred to as the tagless, direct-mapped predictor which is simpler and has faster access time. The tagless predictor can offer comparable performance to current set-associative designs since removal of tags allows more resources to be allocated for the predictor and branch target buffer (BTB). Removal of tags also decouples the per-address predictors from the BTB, thus allowing the two components to be optimized individually. Furthermore, our results show that this tagless implementation is more accurate because it handles conflict misses in the branch history table better. Finally, we examine the system cost-benefit for tagless per-address predictors across a wide design space using equal-cost contours. We study the sensitivity of performance to the workloads by comparing results from the Instruction Benchmark Suite (IBS) and SPEC CINT95. Our work provides principles and quantitative parameters for optimal configurations of such predictors.
Vibration Testing and Modal Analysis of Airplanes – Recent Advances (2004)

&lt;div class="htmlview paragraph"&gt;The paper will introduce some recent advances in vibration testing and modal analysis of airplanes. Recently, a very promising parameter estimation method became available, that has the potential to become the new standard. The main advantage of this so-called PolyMAX method is that it yields extremely clear stabilization diagrams even for broadband and high-order analyses. The method will be applied to two aircraft cases: a Ground Vibration Test using broadband shaker excitation on a small composite aircraft and in-flight data using natural turbulences as excitation. These two data sets allow illustrating both the classical Frequency Response Function based as well as the operational output-only modal analysis process.&lt;/div&gt;
Protective role of olesoxime against wild‐type α‐synuclein‐induced toxicity in human neuronally differentiated <scp>SHSY</scp>‐5<scp>Y</scp> cells (2014)

Because ASYN is a common underlying factor in many cases of PD, olesoxime could be a promising therapy to slow neurodegeneration in PD.
Identification of a Threshold for Skeletal Muscle Injury (1994)

This study was designed to detect the first evidence of injury to muscle induced by passive stretching. Rabbit extensor digitorum longus and tibialis anterior skeletal muscles were subjected to passive stretching at set force levels of 20% or 30% of load to failure. Both tibialis anterior and extensor digitorum longus muscles that were stretched to 30% exhibited no difference in the three tensile parameters when compared with their contralateral control specimens. Maximum contractile force was decreased after stretching. Tibialis anterior and extensor digitorum muscles that were stretched to 20% of control failure force showed no decrement in the tensile parameters or maximum contractile force. Histology of the extensor digitorum longus muscles stretched to 30% of failure force showed small focal areas of muscle fiber rupture and hemorrhage near the distal myotendinous junction. Tibialis anterior and extensor digitorum longus muscle-tendon units stretched to 30% of failure force suffered functional injury as their contractile ability decreased after stretching. In contrast, muscle-tendon units stretched to 20% of failure force suffered no decrement in contractile ability; therefore, a threshold for passive muscle stretch injury has been found. Furthermore, changes in contractile properties and histologic assessment appear to be more sensitive predictors of injury than measurement of structural failure properties.
‘Keratolytic’ Properties of Benzoyl Peroxide and Retinoic Acid Resemble Salicylic Acid in Man (2006)

after 3 h, bp was significantly more effective in disrupting sc cohesion than sa and ra, indicating bp is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.
Using the middle tier to understand cross-tier delay in a multi-tier application (2010)

Understanding the cause of poor performance in a multi-tier enterprise application is challenging, because a performance bottleneck on any tier may cause the whole system to be under utilized, and to fail its throughput or quality of service goals. This paper presents an approach that focuses on the application server to identify bottlenecks in a multi-tier application that are caused by tiers other then the application server. The approach uses a performance tool, named SLICE, that selectively tracks method invocations that cross tier boundaries, and extracts contextual information associated with these invocations. SLICE also collects information from the operating system's scheduler to determine when a thread is blocked. Using the contextual information from method invocations and the information of when a thread is blocked from the operating system, SLICE computes cross tier delay. Experiments on DayTrader, a multi-tier application, show that performance bottlenecks caused by clients or database servers can be identified using cross tier delay.
Primary Extradural Tumors of the Spine - Case Review with Evidence-guided Management (2014)

Primary extradural spine tumors pose significant challenges to surgeons as the aim is to achieve satisfactory surgical outcomes with clean tumor margins (e.g, thus avoid recurrence) while minimizing morbidity. Improvements in radiotherapy, chemotherapy, and novel molecular drugs may increase survival rates and improve overall outcomes.
New strategies in managing and preventing atherosclerosis: focus on HDL. (2002)

The development of atherosclerosis is a complex process whose central elements include the entrapment of low-density lipoprotein in the vessel wall, its subsequent oxidative modification, and the stimulation of proinflammatory gene expression leading to inflammatory cell recruitment, infiltration, and activation. High-density lipoprotein interacts with this process at multiple points, and these interactions could provide therapeutic targets to prevent, stabilize, or even promote the regression of atherosclerosis. High-density lipoprotein may retard atherosclerotic progression by promoting cholesterol efflux from the arterial wall, thereby reducing plaque lipid content as well as potentially inhibiting nascent fatty streak formation. A growing body of evidence derived from clinical trials supports the contention that the raising of high-density lipoprotein levels may confer significant cardiovascular benefit independently of low-density lipoprotein lowering. An antiatherogenic strategy focusing on high-density lipoprotein and its apolipoproteins represents a new frontier in the management of atherosclerosis.
Willow Short‐Rotation Production Systems in Canada and Northern United States: A Review (2014)

Willow ( Salix spp.) short‐rotation coppice (SRC) systems are becoming an attractive practice because they are a sustainable system fulfilling multiple ecological objectives with significant environmental benefits. A sustainable supply of bioenergy feedstock can be produced by willow on marginal land using well‐adapted or tolerant cultivars. Across Canada and the northern United States, there are millions of hectares of available degraded land that have the potential for willow SRC biomass production, with a C sequestration potential capable of offsetting appreciable amounts of anthropogenic greenhouse gas emissions. A fundamental question concerning sustainable SRC willow yields was whether long‐term soil productivity is maintained within a multi‐rotation SRC system, given the rapid growth rate and associated nutrient exports offsite when harvesting the willow biomass after repeated short rotations. Based on early results from the first willow SRC rotation, it was found that willow systems have relatively low nutrient demands, with minimal nutrient outputs other than in the harvested biomass. Our overall aim was to summarize the literature and present findings and data from ongoing research trials across Canada and the northern United States examining willow SRC system establishment and viability. The research areas of interest are the crop production of willow SRC systems, above‐ and belowground biomass dynamics and the C budget, comprehensive soil–willow system nutrient budgets, and soil nutrient amendments (via fertilization) in willow SRC systems. Areas of existing research gaps were also identified for the Canadian context.
Application of Rheological Models to Modified Roofing Asphalts (2011)

Abstract The increased understanding of material behavior with rheology has existed for approximately 80 years as a science and has been applied to roofing products for over 50 years. With asphalt binders, several techniques exist for understanding rheology via the use of models. One of the best recognized models for the evaluation of the rheology of unmodified asphalt binders is the Christensen-Anderson model, and various developments of that model have occurred, enabling its use with filled systems such as those used in roofing applications. In addition to this model, the Rowe-Baumgardner-Sharrock model (developed by the authors) is introduced as an alternate method for defining the properties of roofing products that exhibit visco-elastic solid properties. When rheological data are fitted to master curve functional forms, changes in the model parameters can be rapidly visualized. The performance of various products can be assessed using this technique and can be related to the rheological parameters developed from this model (for example, the rheological index, crossover frequency, etc.). An analysis of the data is presented that includes testing using various rheometers over a wide range of temperatures. These data have been combined into a single master curve and plotted in various formats. The data show how the rheological index and the crossover frequency of the materials change over time, particularly with aging. Performance products can then be assessed and evaluated from both the historical data and models that enable the prediction of cracking and deformation. Adiscussion of the key parameters and a trend analysis are shown. Furthermore, the analysis is applied toward understanding the effectiveness of polymer networks in the roofing materials. As materials age, their properties change, and this can be observed, allowing the study of the effects of polymer network degradation with aging. This paper offers some further understanding of how key rheological parameters change.
(+)-1-[(<i>R</i>)-3,3,3-Trifluoro-2-methoxy-2-phenylpropionyl]-4-(4-{[(2<i>R</i>,4<i>S</i>)-2-(2,4-dichlorophenyl)-2-(1<i>H</i>-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine methanol solvate (2005)

The crystal structure and absolute configuration of the title compound, C34H33Cl2F3N4O5·CH4O, were determined to examine the validity of van 't Hoff's principle of additivity of optical rotations. The conformation of the dioxolane ring is halfway between an envelope, with the flap at the unsubstituted C atom, and a form twisted about Cmethyl­ene—O. The methanol mol­ecule is hydrogen bonded via the OH group to the unsubstituted N atom of the imidazole group.