gebhart/patrepeval huggingface dataset:
Identifying Musculoskeletal Pain Generators Using Molecular Imaging (2021)

Identifying the source of one's pain has been a significant clinical challenge since the physical sensation of pain is felt to be subjective in nature and difficult to quantify. Also referred to as “pain drivers” or “pain generators,” diagnosing the source of pain is complicated by a lack of tools sufficiently sensitive and specific enough to pinpoint the location. Additionally, the experience of pain is not only modulated by the individual's threshold to painful stimuli but also a product of the individual's affective contributions, such as fear, anxiety, and previous experiences. Perhaps then to quantify and localize pain generators is to examine the degree of nociception and pronociceptive inflammation—that is, the extent of cellular, chemical, and molecular changes that occur in pain generating processes. Measuring changes in the local density of receptors, ion channels, mediators, and inflammatory/immune cells that are involved in the painful phenotype using targeted, highly sensitive, and specific molecular imaging approaches is, therefore, a promising approach toward objectively identifying peripheral pain generators. There are a growing number of ongoing clinical and preclinical imaging approaches, especially with inflammatory or pain-related positron emission tomography (PET) radiotracers, that can measure the degree of target concentration and thus serve as a readout for sites of pain generation. Further, when PET is combined with the spatial and contrast resolution afforded by MRI, nuclear medicine physicians and radiologists can potentially identify pain drivers with greater accuracy and confidence. Several of these molecular imaging approaches that are currently being developed to isolate the source of pain are described herein.
Dear Pictograph: Investigating the Role of Personalization and Immersion for Consuming and Enjoying Visualizations (2020)

Much of the visualization literature focuses on assessment of visual representations with regard to their effectiveness for understanding data. In the present work, we instead focus on making data visualization experiences more enjoyable, to foster deeper engagement with data. We investigate two strategies to make visualization experiences more enjoyable and engaging: personalization, and immersion. We selected pictographs (composed of multiple data glyphs) as this representation affords creative freedom, allowing people to craft symbolic or whimsical shapes of personal significance to represent data. We present the results of a qualitative study with 12 participants crafting pictographs using a large pen-enabled device and while immersed within a VR environment. Our results indicate that personalization and immersion both have positive impact on making visualizations more enjoyable experiences.
Improvement of near-field mastering with a 266 nm laser (2003)

Recently the blue-violet laser diode has enabled the recording and readout of high-density optical discs with recording capacity of about 25 gigabytes (GB) in the size of Compact Disc (CD). On a rewritable disc, the groove structure is preformatted. It can be formed even with a conventional 266 nm far-field mastering process. As for a read only memory (ROM) disc, small-pit patterns must be preformatted. Making those patterns requires a smaller spot size for exposure than can be obtained by the conventional far-field process.
Assessing and minimizing time-dependent inhibition of cytochrome P450 3A in drug discovery: A case study with melanocortin-4 receptor agonists (2008)

1-[(2R)-2-([[(1S,2S)-1-amino-1,2,3,4-tetrahydronaphthalen-2-yl]carbonyl]amino)-3-(4-chlorophenyl)propanoyl]-N-(tert-butyl)-4-cyclohexylpiperidine-4-carboxamide (1) is a potent melanocortin-4 receptor agonist that exhibited time-dependent inhibition of cytochrome P450 (P450) 3A in incubations with human liver microsomes. In incubations fortified with potassium cyanide, a cyano adduct was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis as a cyanonitrosotetrahydronaphthalenyl derivative. The detection of this adduct suggested that a nitroso species was involved in the formation of a metabolite intermediate (MI) complex that led to the observed P450 inactivation. Further evidence supporting this hypothesis derived from incubations of 1 with recombinant P450 3A4, which exhibited a lambda(max) at approximately 450 nm. The species responsible for this absorbance required the presence of beta-nicotinamide adenine dinucleotide phosphate reduced form (NADPH), increased with increasing incubation time and decreased following the addition of potassium ferricyanide to the incubation mixture, suggestive of an MI complex. Similar results were obtained with rat liver microsomes and with recombinant P450 3A1. When rats were dosed with indinavir as a P450 3A probe substrate, plasma exposure to indinavir increased three-fold following pretreatment with 1, consistent with drug-drug interaction projections based on the k(inact) and K(I) parameters for 1 in rat liver microsomes. A similar approach was used to predict the magnitude of the corresponding drug-drug interaction potential in humans dosed with a drug metabolized predominantly by P450 3A, and the forecast area under the curve (AUC) increase ranged from four- to ten-fold. These data prompted a decision to terminate further evaluation of 1 as a development candidate, and led to the synthesis of the methyl analogue 2. Methyl substitution alpha to the amino group in 2 was designed to reduce the propensity for formation of a nitroso intermediate and, indeed, 2 failed to exhibit time-dependent inhibition of P450 3A in human liver microsomal incubations. This case study highlights the importance of mechanistic studies in support of drug-discovery and decision-making processes.
Impact of Conditioning Regimen on Outcomes for Patients with Lymphoma Undergoing High-Dose Therapy with Autologous Hematopoietic Cell Transplantation (AutoHCT) (2014)

High-dose therapy with AutoHCT is a standard component of therapy for many patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Choice of high-dose therapy regimens has historically been driven by institutional tradition. No randomized prospective clinical trials have shown a difference in outcomes between conditioning regimens.
MACOP-B Regimen in Non-Hodgkin's Lymphoma (1992)

Two university centers in Finland used MACOP-B regimen as first-line treatment of intermediate and high-grade non-Hodgkin's lymphomas in 1986-1990. The clinical records of all 41 patients treated with this regimen were analyzed. The median age was 47 years (range 16-65), 24% of the patients had WHO performance status > 1, 49% had B-symptoms, 46% had Ann Arbor stage III or IV disease, and 39% had bulky disease. Twenty-three (58%) of the 40 patients who were evaluable for response had CR. The survival rate 36 months after the start of MACOP-B was 62%, but failure-free survival rate only 36%. Among several analyzed factors a lactate dehydrogenase level < 500 U/l before treatment showed the strongest association to failure-free survival. The planned dose intensity was not achieved mainly because of toxicity, and the ratio of the actual dose intensity given to the planned dose intensity varied for the different drugs between 0.77 and 0.92.
The effect of standing vs. variants of the seated position on lumbar intersegmental angulation and spacing: a radiographic study of 20 asymptomatic subjects (2018)

If segmental flexion and segmental loading are the important biomechanical correlates of pain on sitting, such patients should be most comfortable in a kneeling chair, which most closely approximates the standing position. These basic findings will allow better assessment of different seating positions from an ergonomic perspective, and hopefully lead to improvements in chair design.
Isolation and characterization of the gene for the murine T cell differentiation antigen and immunoglobulin-related molecule, Lyt-2 (1987)

We present here the sequence of the 5310 base pair Hind III-cleaved genomic DNA segment that includes the gene for the Lyt-2, a murine differentiation antigen expressed on most immature T lymphocytes as well as the cytotoxic suppressor T cell subset. We also present the complete intron/exon structure of Lyt-2. There are five exons: a fused leader and immunoglobulin variable region like exon, a hinge region exon, a transmembrane exon and two alternatively spliced intracytoplasmic exons (alternative splicing of these exons yields the 38 kDa alpha and 34 kDa alpha' Lyt-2 polypeptides). The promotor region contains a "TATA" box and sequences homologous to the putative immunoglobulin transcriptional control elements cd/pd. S1 protection analysis reveals that thymocytes, T cells from lymph nodes, and a Lyt-2 transfectant obtained by introduction of total genomic DNA have the same initiation site. In the 3' region, there is a polyadenylation signal sequence after a 700 bp long 3' untranslated region.
Design of fragment-derived, covalent inhibitors of SARS-CoV-2 main protease (2020)

This study discusses two potential inhibitors of SARS-CoV-2 main protease, in which warheads (aldehyde and nitrile) capable of reversible covalent bond formation to the catalytic cysteine, are linked to a fragment-derived inhibitor. The PDF file for to the article and the PDB format structure file with the proposed binding modes are provided.<br>
Instillation of liposomes vs dimethyl sulphoxide or pentosan polysulphate for reducing bladder hyperactivity (2009)

Intravesical liposomes and PPS have a beneficial effect in a bladder hyperactivity rat model, while acute instillation of DMSO does not. Intravesical liposomes were effective in doubling the ICI compared with PPS, and might be a new treatment option for bladder hyperactivity.
A versatile queueing model applicable in IP traffic studies (2000)

In this report we consider a single-server discrete-time queueing system, where each source is modeled as a correlated 2-state Markovian packet arrival process, and a generally distributed packet length. For this model, we will study three important quantities, namely the number of packets in the buffer, the amount of work in the buffer, and the packet delay. In particular, for each of these quantities, we will derive an expression for their steady-state probability generating function. From these results, we can then obtain closedform expressions for a number of interesting performance measures such as the mean value, variance, and tail distribution of buffer contents, unfinished work, and packet delay. In addition to the analysis of the system, a lot of emphasis is put on finding closed-form expressions for these quantities that reduce all numerical calculations to an absolute minimum, at the expense of introducing approximations for a number of boundary probabilities that must normally be calculated by solving a set of linear equations. (*) SMACS : Stochastic Modeling and Analysis of Communication Systems This work was sponsored by the Flemish Institute for the Promotion of Scientific and Technological Research in the Industry (IWT).
Choice of Buffer Solution for Stainless Steel OCTG Materials at Laboratory Corrosion Test to Carry Out SSC and SCC Resistance (2017)

Abstract Corrosion environment in oil and gas well is very stable and can be regarded as equilibrium state. Therefore, pH is stable at each depth from wellhead to bottomhole. Buffer solution should be used for laboratory test to appropriately evaluate corrosion resistance for OCTG materials, and the stability of buffer solution, which corresponds to the capability to keep targeting pH throughout test duration, is important to carry out laboratory corrosion tests. From the viewpoint of buffer stability, this paper reviews a theoretical background of buffer solution for stainless steel OCTG materials at laboratory corrosion test, and then the concept is applied to NACE-TM0177-based solution and their modified solutions: (1) Solution-A-based buffer solution (0.5%CH3COOH with added CH3COONa), (2) Solution-B-based buffer solution (2.5%CH3COOH + 0.41%CH3COONa with added CH3COOH or CH3COONa), (3) Solution-C-based buffer solution with CH3COOH (0.4g/L CH3COONa with added CH3COOH and (4) genuine Solution-C buffer solution (0.4g/L CH3COONa with added HCl or NaOH), in addition to 1bar-CO2-satutated NaHCO3 buffer solution and high-pressurized CO2-satutated solution. It is theoretically shown that the pH in the above buffer solution is based on molarity ratio of [CH3COOH]/[CH3COO-], and the stability of each buffer depends on magnitude of molar concentration of acetic acid and/or acetate. In other words, buffer solution is more stable in rich-rich pair of acetic acid and acetate than in lean-lean pair. Among investigated conditions, richer-richer pair of Solution-B-based buffer solution is most stable, and genuine Solution-C (recommended in NACE MR0175/ ISO15156) is less stable than high-pressurized CO2-saturated condition which is likely to be expected in oil/gas well. When using genuine Solution-C, stainless steel is evaluated too severely (too conservatively) in some cases, because the buffering stability is too weak at a certain pH to mitigate pH decrease at bottom of pitting corrosion. Buffered solution for laboratory test should simulate high-pressurized CO2-saturated environment occurring in real oil and gas well, or rather, should be slightly severe condition. At higher pH, the gap in buffering stability is likely to expand between genuine Solution-C and high-pressurized CO2-saturated environment. For accurate SSC evaluation, a careful attention should be paid to appropriate choice of buffer solution for stainless steel in terms of simulation for high-pressurized CO2-saturated environment occurring in oil and gas well.
ABRF Award Winner Innovative Technology for the Study of Cell Signaling. (2007)

This lecture will focus on three different aspects of cell signaling and the mass-spectrometry technologies developed to study them. Presented first will be results of studies to elucidate the “histone code,” complex patterns of post-translational modifications on histone proteins that regulate gene expression, gene silencing, DNA damage repair, and stem cell differentiation, and that block reprogramming of a somatic cell nucleus by an enucleated oocyte. The same modifications also facilitate heritable changes in phenotype that do not involve mutation of DNA (epigenetics). To study these post-translational modifications, we constructed the prototype for the commercially available, tandem linear ion trap/FTMS instrument and also developed methodology that makes it possible to analyze intact proteins on a chromatographic time scale (1 protein/2–5 sec). Proteins are converted to gas-phase, positive ions by electrospray ionization and then allowed to react with fluoranthene radical anions. Electron transfer to the multiply charged protein promotes random fragmentation of amide bonds along the protein backbone. Multiply charged fragment ions are then deprotonated in a second ion/ion reaction with the carboxylate anion of benzoic acid. The m/z values for the resulting singly, doubly, and triply charged ions are used to read a sequence of 15–60 amino acids at both the N- and C- termini of the protein. This information, along with the measured mass of the intact protein, is used to identify unknown proteins, to confirm the amino acid sequence of a known protein, to detect post-translational modifications, and to determine the presence of possible splice variants. Part two of the presentation will describe results of studies to define sites of phosphorylation that regulate the formation of focal adhesions involved in cell migration. For this work, we employ immobilized metal affinity chromatography (IMAC ) to identify phosphorylaton sites present at levels as low as 0.1% of the parent protein. Stable isotopes are employed to follow changes in site usage as a function of cellular perturbation. Further information on this topic is available at cellmigration.org (site guide, phosphoproteomics). Part three of the presentation will focus on signaling between cancer cells and cytotoxic killer cells by the class I antigen-processing pathway. Since signal transduction pathways in cancer cells are highly dysregulated, we hypothesized that this might manifest itself in the presentation of unique phosphopeptides to the immune system in association with Class I major histocompatibility complex molecules. By using a combination of IMAC, stable isotope labeling, and nano-flow HPLC-tandem mass spectrometry, we are now able to detect cancer-specific phosphopeptides present at levels as low as one to five copies per/cell. Results of studies to use these phosphopeptides as immunotherapeutics and/or vaccines against cancer will be discussed.
Cruise Controller with Fuel Optimization Based on Adaptive Nonlinear Predictive Control (2016)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Automotive cruise control systems are used to automatically maintain the speed of a vehicle at a desired speed set-point. It has been shown that fuel economy while in cruise control can be improved using advanced control methods. The objective of this paper is to validate an Adaptive Nonlinear Model Predictive Controller (ANLMPC) implemented in a vehicle equiped with standard production Powertrain Control Module (PCM). Application and analysis of Model Predictive Control utilizing road grade preview information has been reported by many authors, namely for commercial vehicles. The authors reported simulations and application of linear and nonlinear MPC based on models with fixed parameters, which may lead to inaccurate results in the real world driving conditions. The significant noise factors are namely vehicle mass, actual weather conditions, fuel type, etc. In the ANLMPC approach, the vehicle and fuel model parameters are adapted automatically, so accuracy of the prediction is ensured. The adaptation is implemented by a Recursive Least Square (RLS) algorithm and the numerical robustness is improved by adopting Bierman’s implementation with exponential/directional forgetting, and with suitable RLS stopping condition. The ANLMPC has been validated in real world driving conditions running in a production PCM module of a Sport Utility Vehicle (SUV), showing up to 2.4% fuel economy improvement in average compared to the production cruise controller with the same time of arrival. It has been confirmed that the ANLMPC can be run in a standard PCM module with single precision arithmetic, together with its other powertrain control functions.&lt;/div&gt;&lt;/div&gt;
Quantifying scour depth in a straightened gravel-bed river with ground-penetrating radar (2018)

In straight gravel-bed river reaches, riverbank erosion can be induced by alternate bars and their associated scours. The maximum scour depth is therefore a key information to design reliable flood protections. However, scour depth cannot be correctly assessed by bathymetric riverbed surveys if scours are filled with sediments at low discharge. In this work, scour depths in a straightened, gravel-bed river with alternate bars is quantified with ground-penetrating radar (GPR) and the riverbed morphology is linked to the subsurface structure. A 4.5 m deep buried scour with an extent of 30 × 100 m is partially imaged by GPR at the front end of the gravel bar next to the riverbank. The non-imaged part of the scour is expected to be much larger and therefore deeper. Additional research is needed to assess how scour location and depth relate with discharge magnitude and gravel bar dynamics.
Dual Dynamic Inference: Enabling More Efficient, Adaptive and Controllable Deep Inference (2019)

State-of-the-art convolutional neural networks (CNNs) yield record-breaking predictive performance, yet at the cost of high-energy-consumption inference, that prohibits their widely deployments in resource-constrained Internet of Things (IoT) applications. We propose a dual dynamic inference (DDI) framework that highlights the following aspects: 1) we integrate both input-dependent and resource-dependent dynamic inference mechanisms under a unified framework in order to fit the varying IoT resource requirements in practice. DDI is able to both constantly suppress unnecessary costs for easy samples, and to halt inference for all samples to meet hard resource constraints enforced; 2) we propose a flexible multi-grained learning to skip (MGL2S) approach for input-dependent inference which allows simultaneous layer-wise and channel-wise skipping; 3) we extend DDI to complex CNN backbones such as DenseNet and show that DDI can be applied towards optimizing any specific resource goals including inference latency or energy cost. Extensive experiments demonstrate the superior inference accuracy-resource trade-off achieved by DDI, as well as the flexibility to control such trade-offs compared to existing peer methods. Specifically, DDI can achieve up to 4 times computational savings with the same or even higher accuracy as compared to existing competitive baselines.
Experimental and computational characterization of the ferric uptake regulator from Aliivibrio salmonicida (Vibrio salmonicida) (2010)

The Ferric uptake regulator (Fur) is a global transcription factor that affects expression of bacterial genes in an iron-dependent fashion. Although the Fur protein and its iron-responsive regulon are well studied, there are still important questions that remain to be answered. For example, the consensus Fur binding site also known as the “Fur box” is under debate, and it is still unclear which Fur residues directly interact with the DNA. Our long-term goal is to dissect the biological roles of Fur in the development of the disease cold-water vibriosis, which is caused by the psychrophilic bacteria Aliivibrio salmonicida (also known as Vibrio salmonicida). Here, we have used experimental and computational methods to characterise the Fur protein from A. salmonicida (AS-Fur). Electrophoretic mobility shift assays show that AS-Fur binds to the recently proposed vibrio Fur box consensus in addition to nine promoter regions that contain Fur boxes. Binding appears to be dependent on the number of Fur boxes, and the predicted “strength” of Fur boxes. Finally, structure modeling and molecular dynamics simulations provide new insights into potential AS-Fur-DNA interactions.
Olomoucine II, New Effective CDK Inhibitor with Strong Cytotoxic Properties (2001)

The cell division cycle is controlled by cyclin-dependent kinases (cdk), which consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A -cyclin H). These proteins are regulated in several ways: subunit production, complex formation, (de)phosphorylation, cellular localization and interaction with various natural protein inhibitors. Recently, a deregulation of cdks has been proved in human primary tumors and in tumor cell lines. The discovery evoked a strong interest in inhibitors of cdk that could play a role in the therapy of cancers. Four types of cdk inhibitors have so far been described: staurosporine, flavopiridole (L86-8275), butyrolactone-1, and purine derivatives.
ChemInform Abstract: Reversible Intercalation of Hexagonal Boron Nitride with Broensted Acids. (2013)

Abstract Thermal drying of suspensions of hexagonal BN with H 2 SO 4 , H 3 PO 4 , and HClO 4 (70—1000 °C) results in nonoxidative intercalation to form stage‐1 compounds.
Effect of a magnetic field on the instability of the nonequilibrium state of superconducting Nb films in the case of tunnel injection of quasi-particles (1981)

The effect of an external magnetic field on the instability of the nonequilibrium state of superconducting films of niobium when there is tunnel injection of quasi-particles has been studied and it was shown that increasing the magnetic field reduces the value of the instability current. (AIP)