gebhart/patrepeval huggingface dataset:
Mechanism of Covalent Binding of Ibrutinib to Bruton’s Tyrosine Kinase revealed by QM/MM Calculations (2020)

&lt;p&gt;Ibrutinib is the first covalent inhibitor of Bruton’s tyrosine kinase (BTK) to be used in the treatment of B-cell cancers. Understanding the mechanism of covalent inhibition is crucial for the design of safer and more selective covalent inhibitors that target BTK. There are questions surrounding the precise mechanism of covalent bond formation in BTK as there is no appropriate active site residue that can act as a base to deprotonate the cysteine thiol prior to covalent bond formation. To address this, we have investigated several mechanistic pathways of covalent modification of C481 in BTK by ibrutinib using QM/MM reaction simulations. The lowest energy pathway we identified involves a direct proton transfer from C481 to the acrylamide warhead in ibrutinib, followed by covalent bond formation to form an enol intermediate. There is a subsequent rate-limiting keto-enol tautomerisation step (DG&lt;sup&gt;‡&lt;/sup&gt;=10.5 kcal mol&lt;sup&gt;-1&lt;/sup&gt;) to reach the inactivated BTK/ibrutinib complex. Our results represent the first mechanistic study of BTK inactivation by ibrutinib to consider multiple mechanistic pathways. These findings should aid in the design of covalent drugs that target BTK and related proteins. &lt;/p&gt;
Improvements to SUGGAR and DiRTlib for Overset Store Separation Simulations (2009)

SUGGAR is a general overset grid assembly capability that is targeted at moving body simulations. DiRTlib is a library that encapsulates the functionality required to perform the overset interpolation and communications required in an overset composite grid solution. This paper describes enhancements that have been made to SUGGAR and DiRTlib to improve the performance and capability for moving body problems. A procedure to adapt the grids to overlap requirements is demonstrated and found effective in reducing or eliminating the orphans due to insufficient overlap. In addition, SUGGAR can also be linked into the flow solver as a library to provide a capability integral to the flow solver. The paper documents the library interface and discusses modifications required to the flow solver to utilize SUGGAR as a library. Finally, a new overset domain connectivity code, Suggar++, is being developed, and this paper briefly discusses the improvements it offers relative to SUGGAR.
Conformality of atomic layer deposition in microchannels: impact of process parameters on the simulated thickness profile (2022)

Unparalleled conformality is driving ever new applications for atomic layer deposition (ALD), a thin film growth method based on repeated self-terminating gas-solid reactions. In this work, we re-implemented a diffusion-reaction model from the literature to simulate the propagation of film growth in wide microchannels and used that model to explore trends in both the thickness profile as a function of process parameters and different diffusion regimes. In the model, partial pressure of ALD reactant was analytically approximated. Simulations were made as function of kinetic and process parameters such as temperature, (lumped) sticking coefficient, molar mass of the ALD reactant, reactant’s exposure time and pressure, total pressure, density of the grown material, and growth per cycle (GPC) of the ALD process. Increasing the molar mass and the GPC, for example, resulted in a decreasing penetration depth into the microchannel. The influence of the mass and size of the inert gas molecules on the thickness profile depended on the diffusion regime (free molecular flow vs. transition flow). The modelling was compared to a recent slope method to extract the sticking coefficient. The slope method gave systematically somewhat higher sticking coefficient values compared to the input sticking coefficient values; potential reasons behind the observed differences are discussed.
CC-3052: A Water-Soluble Analog of Thalidomide and Potent Inhibitor of Activation-Induced TNF-α Production (1998)

Abstract The immunomodulatory drug thalidomide has been shown to be clinically useful in a number of situations due to its ability to inhibit TNF-α synthesis. However, its use is restricted by potentially serious side effects, including teratogenicity and neuorotoxicity; furthermore, insolubility may present problems in terms of systemic bioavailability. Recently, structural modifications of thalidomide have been designed enabling greatly enhanced anti-TNF-α activity in LPS-treated mice. In contrast to thalidomide (LPS-induced TNF-α IC50 ∼200 μM in DMSO) and other analogs tested, one of these compounds, CC-3052 (IC50 ∼1 μM in water), is water soluble. Furthermore, this analog exhibits increased stability in human plasma (t1/2 ∼17.5 vs 1.5 h for thalidomide) and appears to be nontoxic, nonmutagenic, and nonteratogenic. At pharmacologically active levels, cellular proliferation and LPS-induced IL-6 mRNA and IL-12p40 mRNA (as well as IL-1β and IL-6 protein levels) in whole blood cultures were not affected; apparent inhibition of NK activity by CC-3052 was reversed upon addition of exogenous rTNF-α. In addition, IL-10 mRNA and protein levels were increased. These properties are consistent with results indicating inhibition of phosphodiesterase type IV activity by CC-3052. Furthermore, CC-3052 did not increase the degradation rate of macrophage TNF-α transcripts nor inhibit LPS-induced primary macrophage NF-κB activation. Taken together, the potency of selective TNF-α inhibition, water solubility, and increased plasma stability make CC-3052 an excellent candidate for further development and clinical evaluation for the treatment of TNF-α-mediated disease.
Impact of Asphaltene Precipitation and Deposition on Wettability and Permeability (2021)

Asphaltene precipitation and deposition have been a formation damage problem for decades, with the most devastating effects being wettability alteration and permeability impairment. To this effect, a critical look into the laboratory studies and models developed to quantify/predict permeability and wettability alterations are reviewed, stating their assumptions and limitations. For wettability alterations, the mechanism is predominantly surface adsorption, which is controlled by the asphaltene contacting minerals as they control the surface chemistry, charge, and electrochemical interactions. The most promising wettability alteration evaluation techniques are nuclear magnetic resonance, ζ potential, and the use of high-resolution microscopy. The integration of such techniques, which is still missing, would reinforce the understanding of asphaltene interaction with rock minerals (especially clays), which holds the key to developing a strategy for modeling wettability alteration. With regard to permeability impairment, surface deposition, pore plugging, and fine migration have been identified as the dominant mechanisms with several models reporting the simultaneous existence of multiple mechanisms. Existing experimental findings showed that asphaltene deposition is non-uniform due to mineral distribution which further complicates the modeling process. It also remains a challenge to separate changes due to adsorption (wettability changes) from those due to pore size reduction (permeability impairment).
The MasPar scalable Unix I/O system (2002)

Scalable parallel computers require I/O balanced with computational power to solve data-intensive problems. Distributed memory architectures call for I/O hardware and software beyond those of conventional scalar systems. This paper introduces the MasPar I/O system, designed to provide balanced and scalable data-parallel Unix I/O. The architecture and implementation of the I/O hardware and software are described. Key elements include parallel access to conventional Unix file descriptors and a self-routing multistage network coupled with a buffer memory for flexible parallel I/O transfers. Performance measurements are presented for parallel Unix I/O with a scalable RAID disk array, a RAM disk, and a HIPPI interconnect.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhanced Spectral Mode Selection in an Aspheric Extended-Cavity Resonator (2006)

Strong spectral-mode-selection behavior has been observed in a three-mirror solid-state resonator that was constructed by colinearly aligning an aspheric feedback mirror with a standing-wave two-mirror resonator. This spectral mode selection is measured to be much stronger than that predicted by the frequency selection theory of simple Fabry-Perot cavities. Our study shows that the spatial modes and their associated eigenvalues vary at different oscillation wavelengths in a complex extended-cavity resonator. It is the interplay between spatial modes and spectral modes that induces the strong spectral-mode selection
Factors Controlling the Size of Graphene Oxide Sheets Produced via the Graphite Oxide Route (2011)

We have studied the effect of the oxidation path and the mechanical energy input on the size of graphene oxide sheets derived from graphite oxide. The cross-planar oxidation of graphite from the (0002) plane results in periodic cracking of the uppermost graphene oxide layer, limiting its lateral dimension to less than 30 μm. We use an energy balance between the elastic strain energy associated with the undulation of graphene oxide sheets at the hydroxyl and epoxy sites, the crack formation energy, and the interaction energy between graphene layers to determine the cell size of the cracks. As the effective crack propagation rate in the cross-planar direction is an order of magnitude smaller than the edge-to-center oxidation rate, graphene oxide single sheets larger than those defined by the periodic cracking cell size are produced depending on the aspect ratio of the graphite particles. We also demonstrate that external energy input from hydrodynamic drag created by fluid motion or sonication, further reduces the size of the graphene oxide sheets through tensile stress buildup in the sheets.
ABSENCE OF REACTION OF A XENOGENIC ANTI-H-2 SERUM WITH MOUSE EMBRYONAL CARCINOMA CELLS (1978)

A rabbit antiserum raised against papain-solubilized H-2 antigens has been used to investigate the eventual expression of H-2 antigens and related molecules on embryonal carcinoma cells and on other types of mouse cells. No material reacting with this serum could be detected on cells carrying the F9 antigen. It is concluded that no H-2 antigen or cross-reacting material is expressed on these cell types.
ChemInform Abstract: PHOTOCHEMIE DER BENZO(B)THIOPHENE (1970)

Abstract Bei der gleichzeitigen Photolyse der Benzo(b)thiophene (I) und der isomeren 1,2‐Dichlor‐äthylene (II) werden die isomeren Addukte (III) gebildet.
Parallel Finite Element Analysis of Flow and Heat Transfer on PC-Cluster (2003)

In this paper, numerical simulations of a coupling phenomenon including flow of thermal fluid and heat transfer in a solid are performed on a PC-cluster. To simulate the coupling phenomenon, the flow and the heat transfer in solid are computed simultaneously by solving the same governing equations in which the flow velocity in the solid region is set to zero. By using this method, good parallel efficiency is obtained on PC-Clusters. Some problems, which are cooling of a large-scale integration (LSI) package, flow around a heated candlestick and the internal and external flows of two tubes with consideration of heat transfer, are solved. It is confirmed that the coupling phenomenon of flow and heat transfer can be treated easily using this approach on a parallel environment.
Secret key generation using entropy-constrained-like quantization scheme (2016)

Tremendous researches have been carried out on quantization techniques for secret key generation, but there is little consideration about the causes of quantization discrepancy. In fact, the non-reciprocity channel measurements and the unavoidable quantization noise could result in the quantization discrepancy of the quantization bits at the two intended nodes, which has an important effect on the quantizer design. Moreover, these studies ignore the fact that the quantization level should be bounded by the mutual information between the two intended nodes. In this paper, we first analyze the factors of quantization discrepancy and then propose the Entropy-Constrained-like Quantization Scheme (ECQS) to minimize the quantization discrepancy. This scheme mainly focuses on two segments: non-reciprocity balancing and Entropy-Constrained-like optimal quantization. Simulation results show that, with this scheme, the non-reciprocity channel components can be well balanced and the bit mismatch ratio (BMR) is reduced significantly.
Faculty Opinions recommendation of A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. (2001)

Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Abeta42 peptide (the 42-residue isoform of the amyloid-beta peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant beta-amyloid precursor protein (APP) lowered their brain levels of Abeta42. In cultured cells, the decrease in Abeta42 secretion was accompanied by an increase in the Abeta(1-38) isoform, indicating that NSAIDs subtly alter gamma-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Abeta42 peptide levels independently of COX activity and that this Abeta42-lowering activity could be optimized to selectively target the pathogenic Abeta42 species. PMID: 11700559
ChemInform Abstract: Concise Syntheses of the Amaryllidaceae Alkaloids Ungerimine and Hippadine via the Suzuki Aryl‐Aryl Cross Coupling Reaction. (1990)

Abstract The haloindolines (II) are coupled with the o‐formylphenylboronic acid (I) in the presence of a Pd(0) catalyst to give the polycyclic lactams (III).
Deliberative Mini-Publics (2021)

Bringing together ten leading researchers in the field of deliberative democracy, this important book examines the features of a Deliberative Mini-Public (DMP) and considers the contributions that DMPs can make not only to the policy process, but also to the broader agenda of revitalising democracy in contemporary times.
Cooperative reinforcement learning for adaptive power allocation in device-to-device communication (2018)

Mobile devices are an intrinsic part of the Internet of Things (IoT) paradigm. Device-to-device (D2D) communication is emerging as one of the viable solutions for the radio resource optimization in an IoT infrastructure. However, it also comes with the challenges associated with power allocation as it causes severe interference by reusing the spectrum with the cellular users in an underlay model. Therefore, efficient techniques are required to reduce the interference with proper power allocation. In this paper, we propose a cooperative reinforcement learning algorithm for adaptive power allocation in D2D communication which helps to provide better system throughput as well as D2D throughput with less interference. We perform cooperation by sharing the value function between devices and incorporating a neighboring factor. We design our states for reinforcement learning with appropriate application-defined variables which provide a longer observation space. We compare our work with the existing distributed reinforcement learning method and random allocation of resources. Simulation results show that the proposed algorithm outperforms the distributed reinforcement learning and the random allocation both in terms of overall system throughput as well as D2D throughput by adaptive power allocation.
Atomically Precise Clusters of Noble Metals: Emerging Link between Atoms and Nanoparticles (2017)

Atomically precise pieces of matter of nanometer dimensions composed of noble metals are new categories of materials with many unusual properties. Over 100 molecules of this kind with formulas such as Au<sub>25</sub>(SR)<sub>18</sub>, Au<sub>38</sub>(SR)<sub>24</sub>, and Au<sub>102</sub>(SR)<sub>44</sub> as well as Ag<sub>25</sub>(SR)<sub>18</sub>, Ag<sub>29</sub>(S<sub>2</sub>R)<sub>12</sub>, and Ag<sub>44</sub>(SR)<sub>30</sub> (often with a few counterions to compensate charges) are known now. They can be made reproducibly with robust synthetic protocols, resulting in colored solutions, yielding powders or diffractable crystals. They are distinctly different from nanoparticles in their spectroscopic properties such as optical absorption and emission, showing well-defined features, just like molecules. They show isotopically resolved molecular ion peaks in mass spectra and provide diverse information when examined through multiple instrumental methods. Most important of these properties is luminescence, often in the visible-near-infrared window, useful in biological applications. Luminescence in the visible region, especially by clusters protected with proteins, with a large Stokes shift, has been used for various sensing applications, down to a few tens of molecules/ions, in air and water. Catalytic properties of clusters, especially oxidation of organic substrates, have been examined. Materials science of these systems presents numerous possibilities and is fast evolving. Computational insights have given reasons for their stability and unusual properties. The molecular nature of these materials is unequivocally manifested in a few recent studies such as intercluster reactions forming precise clusters. These systems manifest properties of the core, of the ligand shell, as well as that of the integrated system. They are better described as protected molecules or aspicules, where aspis means shield and cules refers to molecules, implying that they are "shielded molecules". In order to understand their diverse properties, a nomenclature has been introduced with which it is possible to draw their structures with positional labels on paper, with some training. Research in this area is captured here, based on the publications available up to December 2016.
Small Batch High Throughput Plasma Activated Magnetron Sputtering System (2013)

Magnetron sputtering offers a flexible and high throughput deposition process for optical coatings. Sputtering uses two or more metal targets, depositing multilayers comprising dielectrics, metals and conductive oxides.
Indirect arthroscopic rotator interval repair (2003)

Repair of the capsular rotator interval has become a successful adjunct to arthroscopic procedures that address glenohumeral instability. This technical note presents a procedure that allows imbrication of the rotator interval in an indirect fashion regardless of pre-existing arthroscopic portals. A monofilament suture is passed percutaneously using a No.18-gauge spinal needle through the inferior portion of the rotator interval capsule. A soft tissue penetrator is passed through the anterior superior portal to retrieve the suture through the superior portion of the rotator interval capsule. A braided suture is then shuttled in the standard fashion. An arthroscopic knot pusher is placed on the inferior limb of the suture and drives this limb below the deltoid and anterior to the capsule to join the second limb for extracapsular fixation. The technique also provides for direct arthroscopic visualization of the repair and does not necessitate entry into the subacromial space. This is a reproducible procedure that allows efficient repair of the rotator interval.
Do nonlinearities play a significant role in short term, beat-to-beat variability? (2002)

Numerous studies of short-term beat-to-beat variability in cardiovascular signals have not resolved the debate about the completeness of linear analysis techniques. This aim of this paper is to evaluate further the role of nonlinearities in short-term, beat-to-beat variability. We compared linear autoregressive moving average (ARMA) and nonlinear neural network (NN) models for predicting instantaneous heart rate (HR) and mean arterial blood pressure (BP) from past HR and BP. To evaluate these models, we used HR and BP time series from the MIMIC database. Experimental results indicate that NN-based nonlinearities do not play a significant role and suggest that ARMA linear analysis techniques provide adequate characterization of the system dynamics responsible for generating short-term, beat-to-beat variability.
Sustainable Chemistry Considerations for the Encapsulation of Volatile Compounds in Laundry-Type Applications (2019)

Microencapsulation of volatile compounds in fabric care products has brought extra value in a variety of laundry-type applications, allowing clothes to release pleasant scents for weeks after their last wash with minimal amounts of fragrance used. Melamine−formaldehyde is the industry standard in this regard, while polyacrylate and polyurea shells are promising candidates for use in commercial laundry-type applications. Harsh storage conditions and demanding release characteristics have limited the number of viable shell wall materials and chemistries for these kinds of applications. This renders nano- and microencapsulation of volatile compounds for laundry-type applications one of the most challenging areas in the encapsulation field. The largest drawback of the current technology is the limited biodegradability of the produced microcapsules, e.g. when leaking via wastewater. This review summarizes the search toward viable, high-performant and sustainable alternatives for the current technology. First, various techniques to encapsulate volatile compounds in this context are overviewed. Recent relevant encapsulation reports using natural and synthetic shell walls are discussed, while controlled release data are included where possible. Finally, a perspective containing insights toward sustainability in the engineering of alternative capsule chemistries is offered.
Mechanisms for Mutual Attested Microservice Communication (2017)

For systems composed of many rapidly-deployed microservices that cross networks and span trust domains, strong authentication between microservices is a prerequisite for overall system trustworthiness. We examine standard authentication mechanisms in this context, and we introduce new comprehensive, automated, and fine-grained mutual authentication mechanisms that rely on attestation, with particular attention to provisioning and managing secrets. Prototype implementations and benchmark results indicate that mutual attestation introduces only modest overheads and can be made to meet or exceed the performance of common but weaker authentication mechanisms in many scenarios.
Statistical analysis of single‐molecule breaking traces (2013)

The focus of the paper by Riccardo Frisenda et al. (pp. 2431–2436) is the statistical analysis of breaking traces in single-molecule junctions. The cover image contains in the foreground an artistic impression of a molecular junction created with the mechanically controlled break junction (MCBJ) technique. The background features a picture of one of the MCBJ setups present in the authors' laboratory. The MCBJ technique allows for the fast and reproducible creation of nanoelectrodes used to contact single molecules. By statistically analysing thousands of conductance traces and current-voltage characteristics it is possible to extract useful information about the electronic properties of single-molecule junctions.