gebhart/patrepeval huggingface dataset:
Synthesis and Evaluation of 2,6-Modified Purine 2′-C-Methyl Ribonucleosides as Inhibitors of HCV Replication (2015)

A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.
Hallmarks of Retroelement Expression in T-Cells Treated With HDAC Inhibitors (2021)

A wide spectrum of drugs have been assessed as latency reversal agents (LRA) to reactivate HIV-1 from cellular reservoirs and aid in viral eradication strategies. Histone deacetylase inhibitors (HDACi) have been studied in vitro and in vivo as potential candidates for HIV-1 latency reversion. Suberoylanilide hydroxamic acid (SAHA) and romidepsin (RMD) are two HDACi able to reverse HIV latency, however studies of potential off-target effects on retroelement expression have been limited. Retroelements constitute a large portion of the human genome, and some are considered “fossil viruses” as they constitute remnants of ancient exogenous retroviruses infections. Retroelements are reactivated during certain disease conditions like cancer or during HIV-1 infection. In this study, we analyzed differential expression of retroelements using publicly available RNA-seq datasets (GSE102187 and GSE114883) obtained from uninfected CD4 + , and HIV-1 latently infected CD4 + T-cells treated with HDACi (SAHA and RMD). We found a total of 712 and 1,380 differentially expressed retroelements in HIV-1 latently infected cells following a 24-h SAHA and RMD treatment, respectively. Furthermore, we found that 531 retroelement sequences (HERVs and L1) were differentially expressed under both HDACi treatments, while 1,030 HERV/L1 were exclusively regulated by each drug. Despite differences in specific HERV loci expression, the overall pattern at the HERV family level was similar for both treatments. We detected differential expression of full-length HERV families including HERV-K, HERV-W and HERV-H. Furthermore, we analyzed the link between differentially expressed retroelements and nearby immune genes. TRAF2 (TNF receptor) and GBP5 (inflammasome activator) were upregulated in HDACi treated samples and their expression was correlated with nearby HERV (MERV101_9q34.3) and L1 (L1FLnI_1p22.2k, L1FLnI_1p22.2j, L1FLnI_1p22.2i). Our findings suggest that HDACi have an off-target effect on the expression of retroelements and on the expression of immune associated genes in treated CD4 + T-cells. Furthermore, our data highlights the importance of exploring the interaction between HIV-1 and retroelement expression in LRA treated samples to understand their role and impact on “shock and kill” strategies and their potential use as reservoir biomarkers.
Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer (2015)

(18)F-NaF/(18)F-FDG PET/CT is superior to whole-body MRI and (99m)Tc-MDP scintigraphy for evaluation of skeletal disease extent. Further, (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI detected extraskeletal disease that may change the management of these patients. (18)F-NaF/(18)F-FDG PET/CT provides diagnostic ability similar to that of a combination of whole-body MRI and bone scintigraphy in patients with breast and prostate cancer. Larger cohorts are needed to confirm these preliminary findings, ideally using the newly introduced simultaneous PET/MRI scanners.
Molecular Mechanisms of Mutations in Factor XIII A-subunit Deficiency: In vitro Expression in COS-cells Demonstrates Intracellular Degradation of the Mutant Proteins (1997)

Factor XIII deficiency is an autosomal recessive bleeding disorder that is largely caused by various mutations in FXIII A-subunit gene. Characteristically, the patients lack both A-subunit activity and antigen in the circulation. Here we have analysed the consequences of four missense mutations (Met242-->Thr, Arg252-->Ile, Arg326-->Gln, Leu498 to Pro) and one stop mutation (Arg661-->Stop) in the FXIII A-subunit gene by expression in COS-cells. After transient transfection each mutant cDNA expressed mRNA at an equal level to the wild type FXIII. However, the mutant polypeptides accumulated in the cells in significantly reduced quantities and demonstrated only very low enzymatic activity. Analysis of immunoprecipitated metabolically labelled polypeptides demonstrated remarkable instability and intracellular degradation of all mutant FXIII proteins. These results verify the deleterious nature of the individual amino acid changes and confirm that protein instability and susceptibility to proteolysis are consequences of the mutations, as predicted from the three-dimensional model of crystallised FXIII A-subunit.
Digitally fabricated ribbed concrete floor slabs: a sustainable solution for construction (2022)

The concrete used in floor slabs accounts for large greenhouse gas emissions in building construction. Solid slabs, often used today, consume much more concrete than ribbed slabs built by pioneer structural engineers like Hennebique, Arcangeli and Nervi. The first part of this paper analyses the evolution of slab systems over the last century and their carbon footprint, highlighting that ribbed slabs have been abandoned mainly for the sake of construction time and cost efficiency. However, highly material-efficient two-way ribbed slabs are essential to reduce the environmental impact of construction. Hence, the second part of this paper discusses how digital fabrication can help to tackle this challenge and presents four concrete floor systems built with digitally fabricated formwork. The digital fabrication technologies employed to produce these slab systems are digital cutting, binder-jetting, polymer extrusion and 3D concrete printing. The presented applications showcase a reduction in concrete use of approximately 50% compared to solid slabs. However, the digitally fabricated complex formworks produced were wasteful and/or labour-intensive. Further developments are required to make the digital processes sustainable and competitive by streamlining the production, using low carbon concrete mixes as well as reusing and recycling the formwork or structurally activating stay-in-place formwork.
Fiber-based multi-beam laser Doppler vibrometer for measuring transient vibrations (2011)

This article presents a novel fiber-based multi-beam laser Doppler vibrometer (LDV). In this design, a single wavelength laser source at 1550 nm combined with several acousto-optic modulators (AOM) form the transmitter head of the LDV. At the receiver side, one single high-speed photo-detector is employed, instead of multiple detectors according to other reported multi-beam laser Doppler vibrometer.1, 2 Utilization of spatial encoding technique allows us to produce transmitted laser beams with different frequency shifts. In this work, a laser source passes through a sequence of totally four AOMs at different regimes, producing a 4×5 laser beam matrix which is then sent onto different points of vibrating targets for measurement. The backscattered light signals are collected back into a single mode fiber by a fiber collimator and combined with a common reference beam. This mixture of optical signals passes through an Erbium Doped Fiber Amplifier (EDFA) before it is detected by a high-speed fiber-based InGaAs photo-detector. With a digital demodulation algorithm implemented in Labview, the phase variations and thus the vibrations of different testing points can be extracted separately from their corresponding frequency bands. The experimental results show it is possible to do a precise vibration measurement on twenty testing points simultaneously using this novel multi-beam LDV.
Multianalyte Chemical Identification and Quantitation Using a Single Radio Frequency Identification Sensor (2006)

We demonstrate an approach for multianalyte chemical identification and quantitation using a single conventional radio frequency identification (RFID) tag that has been adapted for chemical sensing. Unlike other approaches of using RFID sensors, where a special tag should be designed at a much higher cost, we utilize a conventional RFID tag and coat it with a chemically sensitive film. As an example, we demonstrate detection of several vapors of industrial, health, law enforcement, and security interest (ethanol, methanol, acetonitrile, water vapors) with a single 13.56-MHz RFID tag coated with a solid polymer electrolyte sensing film. By measuring simultaneously several parameters of the complex impedance from such an RFID sensor and applying multivariate statistical analysis methods, we were able to identify and quantify several vapors of interest. With a careful selection of the sensing film and measurement conditions, we achieved parts-per-billion vapor detection limits in air. These RFID sensors are very attractive as ubiquitous multianalyte distributed sensor networks.
Three-dimensional light manipulation by gold nanobumps (2014)

The scattering of surface plasmon polariton (SPP) waves can be manipulated by various plasmonic structures. The plasmonic structure composed of arranged subwavelength nanobumps on a gold thin film is the promising structure to manipulation SPP wave. By controlling the geometric shape of the structures, the height, position, and pattern of scattered light from SPP wave can be modulated as desired. A clear single focusing spot can be reconstructed at a specific altitude by a particular curved structure with appropriate curvature and adjacent interspacing of nanobumps. The designed light patterns reconstructed by the focusing spot from the arranged curved structures at a specific observation plane are clearly demonstrated.
Increased Shelf-Life of Fosphenytoin: Solubilization of a Degradant, Phenytoin, through Complexation with (SBE)7M-β-CD (1998)

Fosphenytoin, a water-soluble prodrug of phenytoin, degrades primarily to phenytoin at pH values <8 during long term storage; phenytoin readily precipitates when formed from fosphenytoin due to its limited aqueous solubility. The objective of this study was to develop stable formulations of fosphenytoin in the pH range of 7.4-8. 0 by inhibiting the phenytoin precipitation through complexation with a parenterally safe cyclodextrin, (SBE)7m-beta-CD. Phase solubility studies at 25 degreesC revealed that phenytoin could be effectively solubilized by (SBE)7m-beta-CD both in the presence and absence of 80.6 mg/mL fosphenytoin (as its dihydrate). The binding constants for the phenytoin/cyclodextrin complex were found to be 1073 and 792 M-1 at pH 7.4 and pH 8.0, respectively. Because of the competitive inclusion between fosphenytoin and phenytoin with (SBE)7m-beta-CD, the extent of solubilization of phenytoin was lower, as expected, in the presence of fosphenytoin than in the absence of fosphenytoin, even though the binding constants for the fosphenytoin/cyclodextrin complex were relatively small (41-45 M-1). Initial rates were used to follow the production of phenytoin from fosphenytoin. Zero-order kinetics were observed under all conditions investigated. Phenytoin production rates were followed at 25, 37, and 50 degreesC in the presence of 0.03 or 0.06 M (SBE)7m-beta-CD. It was projected from the solubility of phenytoin and the kinetic information that fosphenytoin shelf lives as high as nine years at 25 degreesC and pH 7.4 in the presence of 60 mM of (SBE)7m-beta-CD might be possible while longer shelf lives might be possible at pH 8.
Ambient circulation surrounding an ablation catheter tip affects ablation lesion characteristics (2023)

A higher endocardial CE flow can decrease RF effectiveness. Cardiac tissue subjected to no endocardial CE flow may also limit RF for 4 mm catheters, but not for OI catheters; these findings may have implications for RF ablation safety and efficacy, especially in the epicardial space without circulating fluid or in the endocardium under varying flow conditions.
Abstract 4398: Maytansinoid release from thioether linked antibody maytansine conjugates (AMCs) under oxidative conditions: Implication for formulation and for ex vivo sample analysis in pharmacokinetic studies (2010)

Abstract Several antibody—maytansinoid conjugates (AMCs) are in various stages of clinical testing, with the most advanced being trastuzumab-DM1 (T-DM1) in Phase III testing. In T-DM1, the maytansinoid, DM1, is linked to the trastuzumab antibody via a non-reducible (“non-cleavable”) thioether bond using the SMCC (N-succinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate) linker. It has been reported that T-DM1 shows evidence of maytansinoid loss in circulation over time based on ex vivo analysis (Liepold, AACR 2009 abstract #2914), and it has been assumed that a slow retro-Michael reaction is the cause of some linker cleavage. In the present study, however, we demonstrate that a more likely source of observed maytansinoid release is a reaction generated ex vivo. In our study, we used a model synthetic compound, DM1-MCC, which has the DM1 maytansinoid linked via a thioether bond like that in T-DM1, and also a thioether-linked AMC. When incubated in human plasma ex vivo, these were found to release maytansinoid sulfonate (DM1-SO3-) under physiological conditions (37°C, pH 7.4) at a slow rate. The formation of an initial sulphenic acid intermediate (RSOH) during β-elimination was confirmed with trapping experiments using dimedone (5,5-dimethyl-1,3-cyclohexanedione). Oxidatively-stressed AMCs and a model substrate with a more hindered thioether made with the maytansinoid DM4 showed a 3-fold increase in rate of sulfoxide formation, but an 8-fold lower rate of β-elimination compared to unhindered thioethers. DM1-MCC and thioether-linked AMCs were incubated at 37°C with thiol-trapping agents, such as 2,2′-dipyridyldisulfide. No release of DM1-thiol was detected under these conditions. In contrast, greater than 20% of conjugated maytansinoid was cleaved from a thioether-linked AMC under oxidative stress conditions (10−6 M H2O2 1 hr, 4°C dialysis, then incubation 18 h at pH 7.4, 37 °C). The present observations suggest that ex vivo thioether oxidation may lead to maytansinoid release from conjugates. This sulfoxide elimination is noted at 37 °C under aqueous conditions and is likely facilitated by the mildly acidic β-hydrogen on the maleimide (pKa ∼ 25). Oxidation of thioethers (such as methionine) is common during protein extraction and concentration, and the present studies underscore the importance of reducing autooxidation of thioether-linked AMCs with regard to sample handling during pharmacokinetic analyses and conjugate formulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4398.
Macromol. Chem. Phys. 12/2010 (2010)

Front Cover: The exact determination of the metal content in hybrid nanoparticles is still a challenge. The cover image presents a reliable method based on inductively coupled plasma–optical emission spectrometry (ICP–OES) established using detailed investigations of the metal content in metal-complex-containing nanoparticles prepared with the miniemulsion technique. Further details can be found in the article by N. Vogel, C. P. Hauser, K. Schuller, K. Landfester, and C. K. Weiss* on page 1355.
Proceedings of the 2004 ACM SIGPLAN/SIGBED conference on Languages, compilers, and tools for embedded systems (2004)

On behalf of the program committee, I am pleased to present this year's program for LCTES: Languages Compilers and Tools for Embedded Systems. Now in its third year as a conference, we received 120 submissions by the firm submission deadline. From those papers, 28 papers were chosen for presentation at this year's conference.Papers were submitted using the free version of CyberChair. Abstracts and full papers were uploaded, manually assigned to the program committee members, and reviewed over a 5-week period. Each paper was assigned to at least three program committee members, according to interest and areas of expertise, and outside reviews were sought where necessary.Because of the inherently interdisciplinary nature of this conference, the program committee is comprised of 23 researchers and practitioners from around the world who offer expertise across the many technical areas that address embedded systems. The general and program chairs participated in the review process, and so are counted as part of the program committee.The program committee convened on the 14th of March in Saint Louis for an all-day meeting to reach consensus on the program. Those members who had a conflict on a paper left the room for that paper's discussion. Program committee members were allowed to submit papers to this conference. Discussion of those papers was conducted at the very end of the meeting, after the status of all other papers was determined. Papers authored by program committee members were judged by the same, high standards applied to all submissions. At the end of the day's meeting, we accepted 28 papers for this year's program from the 120 submissions--an acceptance rate of 23%. Unfortunately, many fine papers could not be accommodated in this year's program.The composition of the program before you is a reasonable sample of the areas in which we received submissions. Sessions on program optimization, cache and other architectural features, benchmarking and software tool synthesis show the ongoing vitality of those areas. Notably, there are two sessions on power management, indicative of the growing importance of that area.
The interaction between fiber PMD and polarization hole burning in long-haul transmission systems (2005)

We show that the effective spectral width of polarization hole-burning is strongly influenced by the transmission fiber's polarization mode dispersion. We give a simplified theory of this effect along with experimental conformation.
Electromagnetic Radiation under Explicit Symmetry Breaking (2015)

We report our observation that radiation from a system of accelerating charges is possible only when there is explicit breaking of symmetry in the electric field in space within the spatial configuration of the radiating system. Under symmetry breaking, current within an enclosed area around the radiating structure is not conserved at a certain instant of time resulting in radiation in free space. Electromagnetic radiation from dielectric and piezoelectric material based resonators are discussed in this context. Finally, it is argued that symmetry of a resonator of any form can be explicitly broken to create a radiating antenna.
Polyamides of 2,5‐bis(amino methyl) 1,4‐dioxane and dicarboxylic acids (1979)

Abstract Novel polyamides of 2,5‐bis(amino methyl) 1,4‐dioxane ( cis/trans ‐BAMD) with adipic/sebacic acids and of 2,5‐bis(carboxy methyl)/2,5‐bis(carboxy) 1,4‐dioxane with 1,6‐hexane diamine have been prepared. Because of the slightly higher conformational flexibility of the 1,4‐dioxane ring in comparison with that of the cyclohexane ring, the BAMD polyamides have lower T g and T m than the corresponding 1,4‐bis(amino methyl) cyclohexane (BAMC) polyamides. The symmetry of the trans ‐dioxane moiety permits high crystallinity in the trans ‐BAMD polymers. The crystallinity T g and T m of the trans polymers are decreased with the incorporation of the cis ‐dioxane moiety which lacks a plane of symmetry. Because of the hydrophilic nature of the dioxane ring, t ‐BAMD‐6 has good moisture‐regain properties, yet is melt processable ( T m = 292°C).
Adaptive phase-locked fiber array with wavefront phase tip-tilt compensation using piezoelectric fiber positioners (2007)

In this paper, we present the recent development of a conformal optical system with three adaptive phase-locked fiber elements. The coherent beam combining based on stochastic parallel gradient descent (SPGD) algorithm is investigated. We implement both phase-locking control and wavefront phase tip-tilt control in our conformal optical system. The phase-locking control is performed with fiber-coupled lithium niobate phase shifters which are modulated by an AVR micro-processor based SPGD controller. The perturbation rate of this SPGD controller is ~95,000 iterations per second. Phase-locking compensation bandwidth for phase distortion amplitude of 2&pi;-radian phase shift is >100Hz. The tip-tilt control is realized with piezoelectric fiber positioners which are modulated by a computer-based software SPGD controller. The perturbation rate of the tip-tilt SPGD controller is up to ~950 iterations per second. The tip-tilt compensation bandwidth using fiber positioners is ~10Hz at 60-&mu;rad. jitter swing angle.
Rhombomeric origin and rostrocaudal reassortment of neural crest cells revealed by intravital microscopy (1995)

ABSTRACT Neural crest cell migration in the hindbrain is segmental, with prominent streams of migrating cells adjacent to rhombomeres (r) r2, r4 and r6, but not r3 or r5. This migratory pattern cannot be explained by the failure of r3 and r5 to produce neural crest, since focal injections of the lipophilic dye, DiI, into the neural folds clearly demonstrate that all rhombomeres produce neural crest cells. Here, we examine the dynamics of hindbrain neural crest cell emigration and movement by iontophoretically injecting DiI into small numbers of cells. The intensely labeled cells and their progeny were repeatedly imaged using low-light-level epifluorescence microscopy, permitting their movement to be followed in living embryos over time. These intravital images definitively show that neural crest cells move both rostrally and caudally from r3 and r5 to emerge as a part of the streams adjacent to r2, r4, and/or r6. Within the first few hours, cells labeled in r3 move within and/or along the dorsal neural tube surface, either rostrally toward the r2/3 border or caudally toward the r3/4 border. The labeled cells exit the surface of the neural tube near these borders and migrate toward the first or second branchial arches several hours after initial labeling. Focal DiI injections into r5 resulted in neural crest cell contributions to both the second and third branchial arches, again via rostrocaudal movements of the cells before migration into the periphery. These results demonstrate conclusively that all rhombomeres give rise to neural crest cells, and that rostrocaudal rearrangement of the cells contributes to the segmental migration of neural crest cells adjacent to r2, r4, and r6. Furthermore, it appears that there are consistent exit points of neural crest cell emigration; for example, cells arising from r3 emigrate almost exclusively from the rostral or caudal borders of that rhombomere.