gebhart/patrepeval huggingface dataset:
Search for the Active Ingredients from a 2‐Aminothiazole DMSO Stock Solution with Antimalarial Activity (2021)

Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme PfIspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from. Solvent- and temperature-dependent studies using HRMS and NMR spectroscopy to monitor the decomposition led to the isolation and in vitro evaluation of several fractions against PfIspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised compounds using SFC purification and correlated the observed activities to them. Due to the unstable nature of the two isolates, it is likely that they undergo further decomposition contributing to the overall instability of the compound.
Confidence Intervals for the Population Mean Tailored to Small Sample Sizes, with Applications to Survey Sampling (2009)

The validity of standard confidence intervals constructed in survey sampling is based on the central limit theorem. For small sample sizes, the central limit theorem may give a poor approximation, resulting in confidence intervals that are misleading. We discuss this issue and propose methods for constructing confidence intervals for the population mean tailored to small sample sizes. We present a simple approach for constructing confidence intervals for the population mean based on tail bounds for the sample mean that are correct for all sample sizes. Bernstein's inequality provides one such tail bound. The resulting confidence intervals have guaranteed coverage probability under much weaker assumptions than are required for standard methods. A drawback of this approach, as we show, is that these confidence intervals are often quite wide. In response to this, we present a method for constructing much narrower confidence intervals, which are better suited for practical applications, and that are still more robust than confidence intervals based on standard methods, when dealing with small sample sizes. We show how to extend our approaches to much more general estimation problems than estimating the sample mean. We describe how these methods can be used to obtain more reliable confidence intervals in survey sampling. As a concrete example, we construct confidence intervals using our methods for the number of violent deaths between March 2003 and July 2006 in Iraq, based on data from the study "Mortality after the 2003 invasion of Iraq: A cross sectional cluster sample survey," by Burnham et al. (2006).
Additive Manufacturing and Topology Optimization Applied to Impeller to Enhance Mechanical Performance (2018)

The need to be more and more competitive is pushing the complexity of aerodynamic and mechanical design to very high levels.New arrangements are required to enhance the current compressor and expander capabilities from all the points of view: aerodynamic, mechanical, rotordynamic, manufacturing.As we are approaching an asymptotic limit in the performance employing traditional design methodologies, it is needed to explore new frontiers to make additional steps in the rotating equipment improvement.Topology optimization combined with Additive Manufacturing is one of the most promising new approaches to further boost the design.During the conceptual design phase, different options can be investigated to identify the best configuration that suits specific requirements.Topology optimization is a totally new approach and it can be a very effective enabler to individuate new paths and strategies, not always straight forward, and to go beyond techniques already consolidated in turbomachinery design, such as parametric and shape optimizations.Together with the description of the design approach, some test cases and manufacturing trials are presented.For instance, the new design shows a reduced of stress level by 25%, decreasing the impeller mass by 20%, resulting in an increase in max allowable speed and overall performance.Particularly interesting is the application of new rotor design produced by Additive Manufacturing for compressors, as impeller wheels are usually closed and can spin at very fast speed.Mechanical performance improvement and weight reduction are of fundamental importance for these rotor architectures and Additive Manufacturing guarantees the manufacturability of unconventional designs and can bring significant benefit from rotodynamic and mass reduction standpoint.The authors have applied Topology optimization to centrifugal compressor impellers, optimizing the region outside of the flow path ("dressing").Through this document an overview of Additive manufacturing (AM) in particular Direct Metal Laser Melting (DMLM) for Inconel 718 (Inc718) alloy.A comparison between the DMLM material and wrought characteristics showing the main tensile differences.Topological optimization design procedure is presented with some practical examples on centrifugal impeller showing geometries easily manufacturable with AM processes.Finally, an AM process capability on a pump impeller is shown to highlight the current technology level for these components.
A Novel CAE Method for Compression Molding Simulation of Carbon Fiber-Reinforced Thermoplastic Composite Sheet Materials (2018)

Its high-specific strength and stiffness with lower cost make discontinuous fiber-reinforced thermoplastic (FRT) materials an ideal choice for lightweight applications in the automotive industry. Compression molding is one of the preferred manufacturing processes for such materials as it offers the opportunity to maintain a longer fiber length and higher volume production. In the past, we have demonstrated that compression molding of FRT in bulk form can be simulated by treating melt flow as a continuum using the conservation of mass and momentum equations. However, the compression molding of such materials in sheet form using a similar approach does not work well. The assumption of melt flow as a continuum does not hold for such deformation processes. To address this challenge, we have developed a novel simulation approach. First, the draping of the sheet was simulated as a structural deformation using the explicit finite element approach. Next, the draped shape was compressed using fluid mechanics equations. The proposed method was verified by building a physical part and comparing the predicted fiber orientation and warpage measurements performed on the physical parts. The developed method and tools are expected to help in expediting the development of FRT parts, which will help achieve lightweight targets in the automotive industry.
Understanding error propagation in GPGPU applications (2016)

GPUs have emerged as general-purpose accelerators in high-performance computing (HPC) and scientific applications. However, the reliability characteristics of GPU applications have not been investigated in depth. While error propagation has been extensively investigated for non-GPU applications, GPU applications have a very different programming model which can have a significant effect on error propagation in them. We perform an empirical study to understand and characterize error propagation in GPU applications. We build a compiler-based fault-injection tool for GPU applications to track error propagation, and define metrics to characterize propagation in GPU applications. We find GPU applications exhibit significant error propagation for some kinds of errors, but not others, and the behaviour is highly application specific. We observe the GPU-CPU interaction boundary naturally limits error propagation in these applications compared to traditional non-GPU applications. We also formulate various guidelines for the design of fault-tolerance mechanisms in GPU applications based on our results.
A Single Noninterleaved Metasurface for High‐Capacity and Flexible Mode Multiplexing of Higher‐Order Poincaré Sphere Beams (2019)

Cylindrical vector vortex beams, a particular class of higher-order Poincaré sphere beams, are generalized forms of waves carrying orbital angular momentum with inhomogeneous states-of-polarization on their wavefronts. Conventional methods as well as the more recently proposed segmented/interleaved shared-aperture metasurfaces for vortex beam generation are either severely limited by bulky optical setups or by restricted channel capacity with low efficiency and mode number. Here, a noninterleaved vortex multiplexing approach is proposed, which utilizes superimposed scattered waves with opposite spin states emanating from all meta-atoms in a coherent manner, counter-intuitively enabling ultrahigh-capacity, high-efficiency, and flexible generation of massive vortex beams with structured state-of-polarization. A series of exemplary prototypes, implemented by sub-wavelength-thick metasurfaces, are demonstrated experimentally, achieving kaleidoscopic vector vortex beams. This methodology holds great promise for structured wavefront shaping, vortex generation, and high information-capacity planar photonics, which may have a profound impact on transformative technological advances in fields including spin-Hall photonics, optical holography, compressive imaging, electromagnetic communication, and so on.
Ultra-high speed 7mohm, 650V SiC half-bridge module with robust short circuit capability for EV inverters (2019)

Ultra-low RdsA SiC JFET technology is used to realize a 7mohm, 650V Stack Cascode switch, rated at >100A, with very fast switching, and 8us rated short circuit capability that is reported here for the first time. These devices meet all the technical requirements for EV inverters, representing the lowest RdsA and highest short circuit rated contemporary switch technology. The devices are assembled in a high performance, low inductance module to demonstrate extremely low switching losses, making the technology suitable for higher frequency DC-DC applications as well.
Donor T Cell Gene Expression and GVHD. (2008)

GVHD is initiated by donor T cell responses to host alloantigens. However, the occurrence and severity of GVHD are not determined solely by the level of histoincompatibility between donor and recipient. Two MHC-identical subjects will display over 50 minor histocompatibility antigen differences. If histoincompatibility is sufficient for triggering GVHD, the rate of GVHD in MHC-matched recipients of allogeneic hematopoietic cell transplantation (HCT) that receive no immunosuppressive agents should be 100%. Under these conditions, however, GVHD is found in only 50% and 73% of mouse and human recipients, respectively. Histoincompatibility is thus necessary but not sufficient to elicit GVHD. We tested the hypothesis that some donors may be “stronger alloresponders” than others, and consequently more likely to elicit GVHD. To this end, we studied the gene expression profiles of CD4 and CD8 T cells from 50 HCT donors using microarrays and qRT-PCR. We found that gene expression profiling before HCT was able to distinguish those donors whose cells caused GVHD from those whose cells did not. The “dangerous donor” trait (GVHD+ recipient) is under polygenic control and is shaped by the activity of genes that regulate TGF-β signaling and cell proliferation. The donor gene profile defined on day 0 shows strong correlation with that of recipient CD4 and CD8 T cells harvested one year post-AHCT. The latter correlation provides compelling evidence that a significant portion of the differential gene profiles between GVHD+ and GVHD– donors is imprinted at the hematopoietic stem cell level. Moreover, stability of the gene expression profiles over a one-year period suggests that the profiles result from inherited genetic traits as opposed to environmental factors. The gene with the best GVHD-predictive accuracy was SMAD3, a key component of the TGF-β pathway. By testing a cohort of 450 subjects using qRT-PCR, we found that amounts of SMAD3 transcripts varied over a 6-fold range. In mice and humans, SMAD3 is constitutively activated (as evidenced by phosphorylation and accumulation in the nucleus) in many leukocyte subsets. We found in mice that induction of TGF-β signaling in donor T cells is an early event following AHCT and that Smad3-deficient donors trigger more severe GVHD than wild-type littermates. These findings strongly suggest that the donor gene expression profile has a dominant influence on the occurrence of GVHD. In allogeneic HCT, the ability to discriminate strong and weak alloresponders using gene expression profiling could help select low-risk donors and permit tailoring GVHD prophylaxis regimens according to the probability of GVHD occurrence.
Establishment of a stable, acetylated microtubule bundle during neuronal commitment (1989)

Two posttranslational modifications of alpha-tubulin, acetylation and detyrosination, are associated with stable microtubule (MT) populations, including those of neuronal processes. We have used a pluripotent embryonal carcinoma cell line, P19, to investigate changes in MT isotype and stability found in MT arrays during neurogenesis. This cell line has an advantage in that both commitment- and differentiation-related events can be observed. Uncommitted P19 cells have minimal arrays of acetylated and detyrosinated MTs. Following neuronal induction with retinoic acid (RA), indirect immunofluorescence microscopy shows that the first MT modifications occur during commitment and before any morphological change is observed. RA-induced cells initially polymerize a temporarily enlarged population of MTs. Included in this population is a new array of acetylated MTs arranged in a bundle of parallel MTs. This bundle is colchicine-stable, although no MT-associated proteins (MAPs) are detectable using a battery of anti-MAP antibodies. Observation of MT arrays with patterns that are intermediate between the early bundles and short neurites suggests that the acetylated MT bundle subsequently extends to form a neurite. MAP 2 is first detected at about the time of neurite extension. However, at this early stage of differentiation, MAP 2 is not yet limited to dendritic processes. This report provides the first evidence that the stable MTs of mature neurons may be initiated during neuronal commitment.
Association of Diabetic Retinopathy and Diabetic Kidney Disease With All-Cause and Cardiovascular Mortality in a Multiethnic Asian Population (2019)

These results suggest that risks of all-cause and CVD mortality were significantly higher in those with DKD and DR, but DKD was more strongly associated with excess risk. The findings underscore the importance of early identification and close monitoring and management of patients with DR and DKD to reduce the risk of death.
Real-Space Investigation of Electrical Double Layers. Potential Gradient Measurement with a Nanometer Potential Probe (2011)

We report measurement of the potential gradient in a nanometer gap between a Au(111) electrode and a gold tip immersed in a NaClO4 solution. A miniaturized potential probe, constructed with a gold tip and an insulator film, oscillates perpendicular to the electrode surface with a small amplitudes and measures the potential gradient in the local solution environment. The potential gradient is measured as a function of gap distance and then integrated over the distance to obtain the interfacial potential profile. When the probe is located far from the electrode surface, the interfacial potential profile decays exponentially with distance, similarly to the potential distribution of an isolated electrical double layer (EDL). At close gap distances, the profile exhibits an inflection point and a sigmoidal bending toward the electrode potential, which might differ somewhat from that of the isolated electrode surface. These features can be attributed to the overlap of the EDLs on the probe and electrode surfaces during the measurement and also to the electron tunneling between the two surfaces at very short distances. It is demonstrated that the potential gradient method detects signals originating exclusively from the interfacial potential component, whereas it effectively filters out time-dependent noises and potential drifts that might be associated with the complicated microscopic structure of the probe apex. This method can measure the potential profile width more accurately than a direct potential reading method, although it cannot quantitatively measure the absolute potential height.
Introducing the Transmon: a new superconducting qubit from optimizing the Cooper Pair Box (2007)

Short dephasing times pose one of the main challenges in realizing a quantum computer. Different approaches have been devised to cure this problem for superconducting qubits, a prime example being the operation of such devices at optimal working points, so-called sweet spots. This latter approach led to significant improvement of $T_2$ times in Cooper pair box qubits [D. Vion et al., Science 296, 886 (2002)]. Here, we introduce a new type of superconducting qubit called the transmon. Unlike the charge qubit, the transmon is designed to operate in a regime of significantly increased ratio of Josephson energy and charging energy $E_J/E_C$. The transmon benefits from the fact that its charge dispersion decreases exponentially with $E_J/E_C$, while its loss in anharmonicity is described by a weak power law. As a result, we predict a drastic reduction in sensitivity to charge noise relative to the Cooper pair box and an increase in the qubit-photon coupling, while maintaining sufficient anharmonicity for selective qubit control. Our detailed analysis of the full system shows that this gain is not compromised by increased noise in other known channels.
Monochromatic CT image representation via fast switching dual kVp (2009)

In a conventional X-ray CT system, where an object is scanned with a selected incident x-ray spectrum, or kVp, the reconstructed images only approximate the linear X-ray attenuation coefficients of the imaged object at an effective energy of the incident X-ray beam. The errors are primarily the result of beam hardening due to the polychromatic nature of the X-ray spectrum. Modem clinical CT scanners can reduce this error by a process commonly referred to as spectral calibration. Spectral calibration linearizes the measured projection value to the thickness of water. However, beam hardening from bone and contrast agents can still induce shading and streaking artifacts and cause CT number inaccuracies in the image. In this paper, we present a dual kVp scanning method, where during the scan, the kVp is alternately switching between target low and high preset values, typically 80kVp and 140 kVp, with a period less than 1ms. The measured projection pairs are decomposed into the density integrals of two basis materials in projection space. The reconstructed density images are further processed to obtain monochromatic attenuation coefficients of the object at any desired energy. Energy levels yielding optimized monochromatic images are explored, and their analytical representations are derived.
Asymmetric Catalysis of the [5 + 2] Cycloaddition Reaction of Vinylcyclopropanes and π‐Systems. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
xCP: Peer-to-Peer content protection (2004)

In this article, we present a new protocol for implementing an authorized domain, a collection of devices that are equally authorized to play content. This is a new direction for content protection schemes that represents a careful balance between the needs and wants of consumers and content owners. Our protocol is a novel application of cryptographic technique known as broadcast encryption in a configuration that had not been explored previously: a peer-to-peer (P2P) network. We discuss the details of a P2P protocol based on broadcast encryption that supports and enforces renewable content protection for home networks. Several technical advantages of this protocol, including lower computational requirements, flexible network topology and support for intermittently connected devices, are given.
Interconnection and electromigration scaling theory (1986)

Interconnections will become the limit in performance and reliability at submicron dimensions. Long-distance interconnections are defined by models based on resistivity, and it is found that more than half of the interconnections will become categorized as such at 0.5 micrometers feature sizes. The resistivity of even less resistive materials, therefore, will become important. A model for analyzing the trends of material usage for interconnections and for projecting design rules is presented. Electromigration is the driving force away from the lowest resistivity silicon compatible material, namely aluminum. Replacements such as gold, however, have technological problems and the resistivity of refractory metals will be too high for a large fraction of the interconnections. Layered structures are one possible solution to the problems of electromigration.
Design, Synthesis, and Evaluation of [18F]T-914 as a Novel Positron-Emission Tomography Tracer for Lysine-Specific Demethylase 1 (2021)

Histone methylation is associated with the pathophysiology of neurodevelopmental disorders. Lysine-specific demethylase 1 (LSD1) catalyzes histone demethylation in a flavin adenine dinucleotide (FAD)-dependent manner. Thus, inhibiting LSD1 enzyme activity could offer a novel way to treat neurodevelopmental disorders. Assessing LSD1 target engagement using positron-emission tomography (PET) imaging could aid in developing therapeutic LSD1 inhibitors. In this study, PET probes based on 4-(2-aminocyclopropyl)benzamide derivatives that bind irreversibly to FAD found in LSD1 were examined. By optimizing the profiles of brain penetrance and brain-penetrant metabolites, T-914 (<b>1g</b>) was identified as a suitable PET tracer candidate. PET studies in nonhuman primates demonstrated that [<sup>18</sup>F]<b>1g</b> had heterogeneous brain uptake, which corresponded to known LSD1 expression levels. Moreover, brain uptake of [<sup>18</sup>F]<b>1g</b> was reduced by coadministration of unlabeled <b>1g</b>, demonstrating blockable binding. These data suggest that [<sup>18</sup>F]<b>1g</b> warrants further investigation as a potential PET tracer candidate for assessing target engagement of LSD1.