gebhart/patrepeval huggingface dataset:
New Formulations and Derivatives of Amphotericin B for Treatment of Leishmaniasis (2006)

The clinical treatment of leishmaniasis is based on a limited number of drugs, which are associated with adverse effects and have already induced resistance. Amphotericin B (AmB), a polyene antibiotic produced by Streptomyces sp, is the only anti-leishmanial drug which has not induced clinical resistance since its discovery in 1956. The limiting factor in the use of AmB is its toxic effects, mainly nephrotoxicity. The maximal dose of AmB for human use is 1.5 mg/kg which sometimes is not sufficient for cure. The mode of action of AmB is associated with its toxicity: it selectively binds to parasite membrane ergosterol but also, to a lesser extent, to human cholesterol. Apart from this mechanism, AmB has immunomodulatory effects, some of them are deleterious. Reduction of the toxic effects by using lipid formulations allows the infusion of higher doses of AmB. Unfortunately, these formulations are relatively expensive and therefore out of reach for patients in need, in the endemic areas. All the existing formulations are given parenterally, which has obvious disadvantages; most important is the need for hospitalization or multiple visits in the clinic. The current efforts to improve AmB are directed at the production of AmB aggregates in liquid solutions, encapsulation with lipid components, and solubilization by binding to soluble polymers. The expected improved treatment resulting from use of the new formulations is based on better pharmacokinetics, reduced toxicity originating from slow release, targeting to the infected organ and an altered pattern of immune responses (related to AmB). Of particular importance are the attempts to produce derivatives for oral treatment, which will decrease costs of hospitalization and improve applicability for children and the elderly population.
A 28-GHz Passive Outphasing Load Modulator in 40-nm GaN (2021)

This paper presents a passive tunable matching network for load-modulation of a power amplifier (PA). With a set of discrete RF switches, different real impedance transformations can be realized to optimize the loadline match of the PA for output power and/or efficiency. To handle high-power, a 40-nm GaN MMIC process was used to realize three RF switches that switch across a ring impedance network. The tunable matching network realizes 15, 50, or 80Ω depending on the switch state with insertion loss (IL) between 1.7 and 3.3 dB at a center frequency of 28 GHz. The GaN devices have a high breakdown point and therefore the network P <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dB</inf> exceeds 33 dBm. The bandwidth of the network exceeds 2.5 GHz.
Restoration of clipped audio signal using recursive vector projection (2011)

This paper proposes signal restoration from clipping effect without prior knowledge. First, an interval of signal including clipped samples is analyzed by recursive vector projection. By analyzing the neighboring samples of the clipped interval and excluding the clipped interval in the analysis of similarity, signal estimation in the clipped interval is estimated as a by-product of the analysis. Since the estimation holds consistency with the neighboring samples, the restored signal does not suffer from click noise. Evaluation of the clipping restoration with various audio signal ascertained that the proposed method improves signal-to-noise ratio.
Rigorous Modeling of Reactive Absorption Processes (2003)

Abstract Absorption of gases in liquid solutions accompanied by chemical reactions, or reactive absorption, represents one of the most important industrial operations. The advantages of this process are enhanced solution capacity, low impurity concentrations up to the ppm range, moderate operation pressure, and selective removal of contaminants. Reactive absorption is based on a combination of various kinetically controlled phenomena, the focus being on the coupling of chemical reactions and mass transfer in multicomponent mixtures. Therefore, the process description using the equilibrium concept is often insufficient and kinetic modeling is required. This paper describes the basics of rigorous modeling of reactive absorption processes. Several case studies are used in order to validate the models. In addition, a discussion of necessary model parameters, like diffusion coefficients and reaction kinetics, is given. A reduced model with lower computation time is obtained via detailed sensitivity analysis. This model is successfully used in dynamic simulations. In this respect, a proper consideration of the film reactions appears to be crucial.
Cortisone, Testosterone, and Aldosterone Reduce Levels of Nerve Growth Factor Messenger Ribonucleic Acid in L-929 Fibroblasts* (1987)

Previous studies have shown that steroid hormones reduce concentrations of nerve growth factor (NGF) in medium conditioned by L-929 fibroblasts (L cells). In this study, we extend those observations and have measured in L cells the effects of hormone treatment on mRNA encoding NGF. L Cells were grown for 3 days in the presence or absence of hormones. NGF in conditioned medium was measured by NGF RIA; NGF mRNA was measured in cell extracts by Northern blot analysis. Cortisone reduced NGF levels in conditioned medium below the limit of detection of the RIA (less than 10% of control values) with an ED50 of 5 X 10(-9) M; NGF mRNA was reduced to 12% of control levels with an ED50 of 1 X 10(-8) M. Reductions in mRNA were maximal within 3 h and were completely reversed 12 h after removal of the hormone. Levels of NGF in conditioned medium were also undetectable in cultures treated with testosterone, and mRNA levels were reduced by 80%; the ED50 for both effects was 4 X 10(-9) M. Aldosterone (1 X 10(-6) M) reduced NGF to below detectable levels and NGF mRNA by 70%. Progesterone and thyroid hormone had no effect on NGF or NGF mRNA. 17 beta-Estradiol reduced levels of NGF in medium by 50%, but had no detectable effect on levels of NGF mRNA. These results suggest that cortisone, testosterone, and aldosterone decrease NGF levels in L cell-conditioned medium by reducing the cellular content of NGF mRNA.
Sentinel-4 combined optial assemblies (2020)

Jena-Optronik has been contracted to develop and build the core main optics of the Sentinel-4/Ultra-violet/Visible/Near-Infrared (UVN) instrument, which comprises a telescope, a UV-VIS spectrometer and a NIR spectrometer. Due to its geo-stationary orbit and its compactness the photon flux seen by the instrument is low. Simultaneously the lens based optics of the instrument set new standards concerning performance. In consequence straylight levels within the instrument need to be reduced to the bare minimum including high quality polishing of the optics as well as manufacturing facilities as well as processes, which reduce the overall allowed contamination of the optical surfaces to be &lt;50ppm for particular and &lt;50ng/cm² molecular contamination.
Rh NPs Immobilized on Phosphonium-based Supported Ionic Liquid Phases (Rh@SILPs) as Hydrogenation Catalysts (2021)

A series of phosphonium-based supported ionic liquid phases (SILPs) was prepared for the immobilization of Rh nanoparticles (Rh@SILP). The influence of systematic variations in the structure of the ionic liquid-type molecular modifiers (anion, <i>P</i>-alkyl chain length) on the formation and catalytic properties of Rh nanoparticles (NPs) was investigated. Both the nature of the anion and the length of the <i>P</i>-alkyl chain were found to have a strong impact on the morphology of the NPs, ranging from small (1.2-1.7 nm) and well-dispersed NPs to the formation of large NPs (9.9-16.5 nm) and/or aggregates. The catalytic properties of the resulting Rh@SILP materials were explored using the hydrogenation of benzylideneacetone and biomass-derived furfuralacetone as model reactions. The changes in ring and C=O hydrogenation activity as a function of the SILP structure and the Rh NPs size allowed for the selective synthesis of products with distinct molecular functionalities.
System design for spectrally encoded video-rate near infrared tomography during magnetic resonance imaging of the breast (2008)

Video rate diffuse tomography can be implemented within the magnetic resonance breast exam. The following paper outlines the basics of a spectrally encoded source set up, being designed and tested for use in breast imaging within a specialized breast surface coil. The system design maximizes input power to the breast, while confining the spectrum to a 10 nm bandwidth of near-infrared light. The center spectral band can be varied, since it is supplied by a tunable Ti:Sapphire laser. The encoding of each source is achieved by splitting the signal into individual nanometer bands through a high resolution grating, and focusing the output of this into each source fiber. This source configuration then requires spectral detection at the output, and so each detection fiber is delivered to a high resolution spectrometer to resolve the detected intensities. Breast imaging with this system has some subtle dynamic range issues, which means that light from sources farthest from the detector pickup are likely not providing useful data, but the closest 4-6 fibers near each source can provide useful data. The implementation of this is being carried out within a magnetic resonance breast array, and initial testing of the signals is shown, along with diagrams and photographs of the system configuration.
Augmented Replicative Capacity of the Boosting Antigen Improves the Protective Efficacy of Heterologous Prime-Boost Vaccine Regimens (2014)

The development of optimal prime-boost vaccine regimens is a high priority for the vaccine development field. In this study, we compared two boosting antigens with different replicative capacities. Boosting with a more highly replicative vector resulted in augmented immune responses and improved protective efficacy.
Accelerated RNA detection using tandem CRISPR nucleases (2021)

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided recognition of RNA that triggers cleavage and release of a fluorescent reporter molecule<sup>1,2</sup>, but long reaction times hamper sensitivity and speed when applied to point-of-care testing. Here we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 RNA copies/microliter in 20 minutes. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that detected SARS-CoV-2 RNA from nasopharyngeal samples with PCR-derived Ct values up to 29 in microfluidic chips, using a compact imaging system. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables direct RNA detection in a format amenable to point-of-care infection diagnosis, as well as to a wide range of other diagnostic or research applications.
Simulation Failure Robust Bayesian Optimization for Estimating Black-Box Model Parameters (2021)

Advances in modeling and computation have resulted in high-fidelity digital models capable of simulating the dynamics of a wide range of industrial systems. These models often require calibration, or the estimation of an optimal set of parameters, to reflect a system’s observed behavior. While searching over the parameter space is an inevitable part of the calibration process, models are seldom designed to be valid for arbitrarily large parameter spaces. Application of existing black-box calibration methods, therefore, often require repeatedly evaluating a model over a wide range of parameters. For some parameter combinations, the simulations could be unreasonably slow or fail altogether. In general, the shape of subregions in the parameter space that could result in simulation failure is unknown and near-impossible to ascertain analytically. In this paper, we propose a novel failure robust Bayesian optimization (FR-BO) algorithm that learns these failure regions from simulation data and informs a Bayesian optimization algorithm to avoid failure regions while searching for optimal parameters. This results in acceleration of the optimizer’s convergence and prevents wastage of time trying to simulate parameters with high failure probabilities.
Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data (2018)

In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data.
Graceful BGP Session Shutdown (2018)

This document standardizes a new well-known BGP community,
GRACEFUL_SHUTDOWN, to signal the graceful shutdown of paths. This
document also describes operational procedures that use this well-
known community to reduce the amount of traffic lost when BGP peering
sessions are about to be shut down deliberately, e.g., for planned
maintenance.
Predicting microporous crystalline polyimides (2009)

We present here structural models for 15 hypothetical crystalline polyimides with an analysis of predicted micropore properties for selected structures.
CRAWDAD dataset dartmouth/campus (v. 2005-03-08) (2005)

This dataset includes syslog, SNMP, and tcpdump data for 3 years or more, for over 450 access points and several thousand users at Dartmouth College.
Extracting heterogeneous structured features from music performance (2011)

In music performance, the musician adds artistic expressive elements beyond the information contained in conventional western music scores. As micro-fluctuations these expressive dimensions convey emotions and essential interpretative information and can be measured and compared quantitatively, over large and small scales, and evaluated for their effect on aspects of the performance. We present a heterogeneous expressive music feature description that include both inter-note features that extend over musical phrases composed of several notes, and intra-note features that represent the internal variations within each musical note. The intra-note features include pitch and pitch deviation, dynamic level, timber, articulation and vibrato. The inter-note features include timing and dynamics, as well as timber, pitch deviation, articulation, and vibrato extending across multiple notes and musical phrases. A complete multi-dimensional feature description for every note is unnecessary because there is a hierarchy of note functions in a musical phrase and certain features may be more or less important depending upon their function in the phrase. Thus, we introduce a heterogeneous representation that affords the flexibility to reflect the hierarchical significance of each note or phase segment. Specific visualization and animation schemes of the proposed representation, to facilitate user interaction with the music, are also presented.
Search for new resonances decaying via WZ to leptons in proton–proton collisions at s=8TeV (2014)

A search is performed in proton-proton collisions at s = 8 TeV for exotic particles decaying via WZ to fully leptonic final states with electrons, muons, and neutrinos. The data set corresponds to an integrated luminosity of 19.5 fb -1 . No significant excess is observed above the expected standard model background. Upper bounds at 95% confidence level are set on the production cross section of a W boson as predicted by an extended gauge model, and on the W WZ coupling. The expected and observed mass limits for a W boson, as predicted by this model, are 1.55 and 1.47 TeV, respectively. Stringent limits are also set in the context of low-scale technicolor models under a range of assumptions for the model parameters.
Mending Broken Hearts: the Future of drug-based Cardiac Regeneration (2007)

Coronary heart disease is a massive health problem worldwide. In the USA alone, 1.2 million people suffer a coronary attack every year, and approximately 40% of these individuals die as a result. As damaged cardiac muscle forms scar tissue and is unable to function properly, those that do survive the attack are often left severely ill. Consequently, the potential for a therapy that allows healthy cardiac muscle to proliferate at the site of injury is enormous. Dr Mark Keating is a leading researcher in this area of regenerative medicine and his group has recently identified a compound that aids in the process of cardiac regeneration. Although currently focussing on ophthalmic drug research at Novartis, Dr Keating still has a great interest in this area. Here he discusses the potential of drug-based cardiac regeneration and the problems that must be overcome before this treatment can reach the clinic.
Defining Cybernetics: Reflections on the Science of Governance (2015)

In this article, we have reconsidered the meaning of cybernetics and provided a taxonomy that can be useful for us to understand various cybernetics more clearly. We have also investigated some fundamental properties of governable or self-governable distributed systems. In particular, we believe that ontology plays a key role for a distributed system to become governable or even self-governable. We think that automatic construction of a good ontology in a distributed system is an interesting topic for further study. In fact, constructing a good ontology for a mobile communication network, a social network, a traffic control network, and any network related to our daily lives is important to make the network governable, safe, and secure. For large-scale distributed systems (e.g., the Internet), certain self-governability is also indispensable for the network to be more reliable or dependable. Of course, full self-governability of these systems may not be expected from the point of view of human beings.
Angiogenesis revisited from a metabolic perspective: role and therapeutic implications of endothelial cell metabolism (2017)

Endothelial cell (EC) metabolism has lately emerged as a novel and promising therapeutic target to block vascular dysregulation associated with diseases like cancer and blinding eye disease. Glycolysis, fatty acid oxidation (FAO) and, more recently, glutamine/asparagine metabolism emerged as key regulators of EC metabolism, able to impact angiogenesis in health and disease. ECs are highly glycolytic as they require ATP and biomass for vessel sprouting. Notably, a regulator of the glycolytic pathway, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3, controls vessel sprouting during the angiogenic switch and its inhibition in tumour ECs leads to vessel normalization, thereby reducing metastasis and ameliorating chemotherapy. Moreover, FAO promotes EC proliferation through DNA synthesis, and plays an essential role in lymphangiogenesis via epigenetic regulation of histone acetylation. Pathological angiogenesis was decreased upon blockade of carnitine palmitoyltransferase 1, a regulator of FAO in ECs. More recently, metabolism of glutamine, in conjunction with asparagine, was reported to maintain EC sprouting through TCA anaplerosis, redox homeostasis, mTOR activation and endoplasmic stress control. Inactivation or blockade of glutaminase 1, which hydrolyses glutamine into ammonia and glutamate, impairs angiogenesis in health and disease, while silencing of asparagine synthetase reduces vessel sprouting <i>in vitro</i> In this review, we summarize recent insights into EC metabolism and discuss therapeutic implications of targeting EC metabolism.
Phase I study of mesothelin-targeted immunotoxin LMB-100 given as a long infusion with or without nab-paclitaxel. (2020)

3553 Background: LMB-100 recombinant immunotoxin consists of a mesothelin-binding Fab for targeting a modified Pseudomonas exotoxin A payload. Previous Phase 1 clinical testing of a 30-minute LMB-100 “short” infusion format identified a serum half-life of ~1 hour. Pre-clinical data suggested that extending infusion time could improve anti-tumor efficacy by increasing tumor cell duration of exposure to LMB-100. The primary objective of this study was to determine the safety and tolerability of administering LMB-100 in a long infusion format over 24-48 hours alone or with nab-paclitaxel chemotherapy in patients with mesothelin-expressing solid tumors. Methods: Patients (n = 15) with pancreatic adenocarcinoma and other mesothelin-expressing solid tumors (n = 3; mesothelioma, colon, and ampullary cancers) treated on 3 dose levels received long infusion of LMB-100 (65 or 100 mcg/kg/day) for 24 hour on Days 1 and 4 (n = 6) or 48 hour on Day 1 (n = 9) with or without a loading dose (40 mcg/kg over 30 minutes) for up to 2 cycles. In the second arm, patients (n = 5) with pancreatic adenocarcinoma were treated with LMB-100 over 24 hours on Day 1 concurrently with nab-paclitaxel (125 mg/m 2 ) for up to 3 cycles. Results: DLT of proteinuria (grade 3) in one patient and acute kidney injury (grade 1) in one patient were observed amongst patients receiving 100 mcg/kg/day over 48 hours and 24 hours, respectively. No objective responses were seen but all patients receiving nab-paclitaxel had &gt; 50% decrease in CA 19-9. Patients at all single agent dose levels (8 of 10 evaluable) developed high titer anti-drug antibodies (ADAs) against LMB-100. Those with ADAs (8 of 8) had undetectable cycle 2 peak plasma LMB-100 concentration. Development of high titer ADAs occurred more frequently with long infusion than seen previously with “short” infusion LMB-100. Most long infusion patients (19 of 20) developed increased serum IL-6 within 24 hours of LMB-100 infusion. However, the systemic inflammatory response to LMB-100 (as measured by increased serum CRP) which occurs in most “short” infusion patients was not observed. Conclusions: Long infusion format LMB-100 is generally well tolerated but immunogenicity limits treatment to 1 effective cycle. No anti-tumor efficacy of the single agent was observed. Clinical trial information: NCT02810418 .
Vacancy defects in as‐grown and nº‐irradiated GaP and GaAs1−xPx Studied by Positrons (1988)

Abstract Measurements of positron lifetime τ and of the shape parameter S of the Doppler‐broadened annihilation line are used to study bulk and defect properties in GaP and GaAs 1− x P x . τ and S decrease linearly with the composition x of GaAs 1− x P x layers. A second lifetime component (τ 2 = 290 ps) observed in as‐grown GaP is attributed to stoichiometric P vacancies. After neutron irradiation of GaP and GaAs 0.13 P 0.87 positrons are trapped by Ga vacancies (τ 2 = 250 ps). These vacancies anneal out in two stages at 200–550 °C and 550–800 °C.