gebhart/patrepeval huggingface dataset:
Quantitative, Real-Time Measurements of Intracellular Target Engagement Using Energy Transfer (2018)

Intracellular target affinity and residence time are fundamental aspects of pharmacological mechanism (Lu and Tonge, Curr Opin Chem Biol 14:467-474, 2010). Although various robust biochemical approaches exist to measure these binding characteristics, analysis of compound binding with isolated targets may not accurately reflect engagement in the milieu of living cells. To realize the influence of cellular context, methods are needed that are capable of quantifying affinity and residence time in the presence of the intracellular factors that may impact target engagement. Bioluminescence resonance energy transfer (BRET) offers a solution for intracellular target engagement when quantitative metrics or kinetic analyses are required.
[The reliability of conclusions based on hair mineral analysis in individual diagnostic]. (2004)

The advantages of ubtaining samples for hair mineral analysis (HMA) as well as the possibility to measure former exposures and in addition to carry out segment analysis make it desirable to work with HMA in order to find a diagnosis. The laboratories which offer HMA differ distinctly in their procedure of analysis and quality control. HMA is generally not usable for individual diagnostic with two exceptions (arsenic and methylmercury) because of the large number of factors of individual and environmental influences and sources of error of the method of analysis. HMA can be used for cadmium, lead, and zinc in order to compare a single person with a larger population. Further research into the relationship of content of elements in hair and other tissues of the body is desirable.
An object‐oriented approach to dynamic service descriptions (1994)

Abstract The former CCITT has defined a methodology, consisting of three stages, to evolve from a set of service descriptions to a protocol definition that supports these services. In the first stage, the service is described from a user's viewpoint. A part of this first stage consists of the descriptions of the dynamic behaviour of the service. The introduction of this paper elaborates on the interpretation of the ‘user's viewpoint’ of dynamic service descriptions. In the subsequent sections we introduce an object‐oriented approach to define a framework for the dynamic service descriptions. The flexible definition of services is facilitated by decomposing the service into a standard set of building blocks, referred to as service objects. A service object is the smallest service element that a user can independently reference and manipulate. By modelling in terms of service objects, we avoid the presumption that the total service consists of a specific number of parties or connections. The definition of a service mainly consists of imposing additional semantic rules on the way service objects can be manipulated within the context of that service. The complete system will thus consist of a servicespecific part and a generic part, i.e. a part which is common to all services. An overview of the system configuration and the behaviour of the generic part is illustrated by SDL Descriptions. Finally, we illustrate the method by describing a typical multiconnection multiparty service. The work presented within this paper is based on the results of the RACE MAGIC project.
Phase 1 clinical trials in 83 patients with pancreatic cancer (2010)

Our results suggest that phase 1 clinical trials offer a reasonable therapeutic approach for patients with advanced pancreatic cancer.
Real-time monitoring of scattered laser light by a single particle of several tens of nanometers in the etching chamber in relation to its status with the equipment (1998)

In order to detect a single particle of several tens of nanometers and to clarify the relationship between particle outbreak and the workings of wafer processing equipment, a scattered laser light measurement system has been produced experimentally. The system is composed of a high frequency pulse-laser oscillator, a two-dimensional charge-coupled device image processor, and a status-signal processor connected to the wafer process equipment. By using this system, in situ monitoring of a single particle of several tens of nanometers that flakes off films deposited on the upper ground electrode of the plasma etching chamber, and observation of its trajectory are successfully demonstrated for real tungsten etchback processing. Moreover, data from the system show that, after processing several hundred wafers, the outbreak of particles in the etching chamber had a correlation with specific workings of the etching equipment, such as turning off the rf power and the injection of purge gas to the chamber. The scattered light measurement system has demonstrated its ability to monitor particle outbreak, transport, and behavior.
Molecular Electrostatic Potential Analysis for Enzymatic Substrates, Competitive Inhibitors, and Transition-State Inhibitors (1996)

Recent advances in the application of kinetic isotope effects to enzyme-catalyzed reactions have provided reliable information for enzymatic transition state structures. A method is presented for quantifying the similarity of substrates and inhibitors with their enzyme-stabilized transition states. On the basis of transition-state stabilization theory for enzymatic reactions, molecules most similar to the transition state structure bind with greatest affinity. Molecular similarity measures are applied to compare substrates, competitive inhibitors, and transition state inhibitors with the transition state structures stabilized by the enzymes AMP deaminase, adenosine deaminase, and AMP nucleosidase. (R)- and (S)-Coformycin 5‘-phosphate are inhibitors for AMP deaminase, with the R-species superior to its enantiomer. Formycin 5‘-phosphate 4-aminopyrazolo[3,4-d]pyrimidine-1-ribonucleotide, and tubercidin 5‘-phosphate inhibit AMP nucleosidase. The transition state for adenosine deaminase is analogous to that for AMP deaminase, allowing analysis of the tight-binding hydrate of purine ribonucleoside and of a weaker inhibitor, 1,6-dihydropurine ribonucleoside. The basis for ranking molecules for similarity to the transition state is the distribution of electrostatic potential at the molecular van der Waals surface. Spatial properties of a molecule are described through the topography of the surface, while the electrostatics capture ionic, hydrogen-bonding, and hydrophobic features. A test molecule is compared with the transition state by orienting the two species so that their van der Waals surfaces are maximally coincident. At this orientation, a single measure sensitive both to the electrostatic potential and its spatial distribution is used to rank the electronic similarity. For AMP deaminase, adenosine deaminase, and AMP nucleosidase, the transition state inhibitors are quantitatively more similar to the transition states than are the substrates. A strong correlation between the binding free energies and the similarity measures is found for most of the transition-state inhibitors in all three enzyme systems. This method is useful in the logical design of transition state inhibitors and may be applied to similarity searches of chemical libraries.
Processing of precursor interleukin 1 beta and inflammatory disease. (1990)

The processing of precursor interleukin 1 beta (IL1 beta) by elastase, cathepsin G, and collagenase, the major proteases released at sites of inflammation, was investigated using recombinant pro-IL1 beta. Each of these proteases cleaved the 31-kDa inactive precursor to a form similar in size and specific activity (greater than 10(8) units/mg) to the 17-kDa mature protein isolated from activated monocytes. Elastase, collagenase, and cathepsin G cleaved the IL1 beta precursor at distinct sites which are amino-terminal to the monocyte-processing site, Ala-117 (Cameron, P., Lumjuco, G., Rodkey, J., Bennett, C., and Schmidt, J. A. (1985) J. Exp. Med. 162, 790-801). Amino-terminal sequencing of the products of digestion by elastase and cathepsin G determined that resultant active IL1 beta proteins contained an additional 13 or 3 amino acids relative to mature IL1 beta. Synovial fluid collected from patients with inflammatory polyarthritis and bronchoalveolar lavage fluid from patients with sarcoidosis supplied similar processing activity(s). Control fluids from patients who had no symptoms of inflammatory disease did not exhibit processing activity. Lavage fluids that processed precursor IL1 beta were demonstrated to contain cathepsin G and/or elastase activity, whereas controls were negative. Because a significant fraction of IL1 beta may be secreted from monocytes as the inactive 31-kDa precursor (Hazuda, D. J., Lee, J. C., and Young, P. R. (1988) J. Biol. Chem. 263, 8473-8479, Bomford, R., Absull, E., Hughes-Jenkins, C., Simpkin, D., and Schmidt, J. (1987) Immunology 62, 543-549, and Mizel, S. B. (1988) in Cellular and Molecular Aspects of Inflammation Poste, G., and Crooke, S., eds) pp. 75-93, Plenum Publishing Corp., New York), these results suggest that in vivo the IL1 beta precursor can be processed after secretion by any of several proteases released at inflammatory sites.
Isolation of the elusive pig islet. (1990)

This study describes a procedure for large scale isolation of swine islets. The reported results are from 15 consecutive isolations. The glands were removed from live animals with no warm ischemia, and the pancreata were digested by a modification of the automated method for human islet isolation. It was possible to separate an average of 690,000 +/- 279,429 islets per pancreas corresponding to 10,360 +/- 4034 islets per gram of pancreas with a volume of 714 +/- 480 mm3. After purification the recovery was 255,000 +/- 32,407 islets corresponding to 4,000 +/- 567 islets per gram of pancreas. Purity of the final preparation was 80% to 95% islets. Insulin content resulted in an average of 146.8 +/- 78 U before purification and 71 +/- 53 U after purification. After a 10 mm3 aliquot of the final preparation was transplanted under the renal subcapsular space of seven nude mice with diabetes, normoglycemia occurred in six of the mice. Thirty days after transplantation, nephrectomy of the kidneys bearing the grafts produced a rapid return to the diabetic state in all cases. This method makes it possible to provide large numbers of intact swine islets for preliminary studies of prevention of the rejection of pig islet xenograft by immunoalteration and immunoisolation procedures.
Auxin-binding site in wheat shoots: Interactions between indol-3-ylacetic acid and its halogenated derivatives (1985)

The specificity of IAA-binding site from the wheat shoots was investigated in an attempt to confirm its receptor function. Several monofluoro-, monochloro-, dichloro- and monobromo-substituted indol-3-ylacetic acids were allowed to displace14C-IAA from the binding site. Displacement abilities of these halogenated IAAs were closely related to there activities in wheat coleoptile straight growth biotest. This finding indirectly confirms thephysiological significance of this binding site.
Microelectronic Bonding Processes Monitored by Integrated Sensors (2002)

Abstract Real‐time monitoring methods are beneficial for the control, optimization, and failure analysis of microelectronic packaging processes. The focus of this chapter is on the real‐time monitoring of two widely used processes, soft solder die bonding and thermosonic ball bonding. The methods presented here use uniquely developed microsensors integrated on custom‐made test chips using commercial double‐metal CMOS processes. For the soft solder die bonding process, nine aluminum‐based resistive temperature detectors were integrated on various locations on a test chip. The temperature was monitored during the placement of the test chip on the leadframe. The experimental results describe the wetting and spreading effects of the molten solder under the drip. Together with numerical results obtained with a transient thermal finite element model, the beginning of wetting can be quantified. For the soft solder PbSn10, wetting occurred around 30 ms after touch down. This method hence can be used to determine wetting times under different process conditions. The wetting time determines an upper limit of the through put of the process. For the thermosonic ball bonding process, temperature and force sensors were integrated on test chips. The sensors are aluminum resistors and piezoresistive p + ‐ and n + ‐diffused resistors placed around bond pads. A bond quality parameter can be derived from the temperature signal variation during bonding. The piezoresistive sensors permit the measurement of forces in the x‐, y‐, and z‐directions simultaneously. The ultrasonic tangential force signal reached a typical value of 0.12 N on a 50μm diameter contact zone and revealed significant process characteristics. Four process phases are identified which are necessary for a successful ball bond formation. These phases are assigned to initial stiction, sliding, bond growth, and deformation effects.
Synthesis of New Heterocycles through a Cation-Driven Tandem Ring-Enlargement−Annulation Reaction (2002)

[reaction: see text] The thionium ion, generated through a cyclopropylcarbinyl-cyclobutyl ring expansion, is, for the first time, intramolecularly intercepted by activated aromatic rings to generate new versatile 2a-methyl-8b-(phenylsulfanyl-1,2a,3,8b-tetrahydro-2H-cyclobuta[c]chromenes.
[O1–13–02]: COGNITIVE VULNERABILITIES IN PRESENILIN‐1 E280A MUTATION‐CARRYING CHILDREN FROM THE WORLD's LARGEST AUTOSOMAL‐DOMINANT ALZHEIMER's DISEASE KINDRED (2017)

Autosomal dominant Alzheimer's Disease (ADAD) mutation carriers will develop early-onset Alzheimer's disease (AD) in the future with near 100% certainty and provide a unique opportunity to characterize the earliest biological changes associated with the predisposition to develop AD. We previously reported that presenilin-1 (PSEN1) E280A mutation–carrying children from the world's largest ADAD kindred in Colombia have structural and functional connectivity MRI abnormalities, along with plasma biomarker findings consistent with Aβ1–42 overproduction. In this study, cross-sectional measures of cognitive, behavioral and socio-emotional functioning were assessed in PSEN1 mutation–carrying children, decades before the kindred's estimated median age 44 of mild cognitive impairment. Two-hundred-sixteen children (108 PSEN1 E280A carriers, 108 non-carriers), aged 8 to 17 years, were recruited from the Alzheimer's Prevention Initiative Colombia Registry. Participants were administered the Evaluacion Neuropsicologica Infantil-ENI, assessing memory, language and attention/executive function, and the Wechsler Intelligence Scale for Children-IV (WISC-IV), measuring general intelligence (verbal and non-verbal abilities, working memory, and processing speed). Parent-Child dyads completed the Behavior Assessment System for Children-2, assessing socio-emotional and behavioral functioning. Families and raters remained blind to the participant's genetic test results. Regression models examined the associations between cognitive and behavioral measurements and age in the mutation carrier and non-carrier groups. Compared to non-carriers, PSEN1 mutation carriers had lower mean scores on the WISC-IV Verbal Comprehension (p=0.01) and Processing Speed domains (p=0.04). Self-report measures revealed lower mean scores for carriers in Interpersonal Relations, skills which are necessary for interacting successfully with peers and adults (p=0.04). Age-associated differences between groups were seen in ENI subtests of attention (p=0.02). There were no differences in memory, complex attention, executive function or other cognitive domains. Results describe the earliest known cognitive and social vulnerabilities associated with ADAD. Findings suggest that children at genetic risk for ADAD have verbal, attention, and social vulnerabilities, even before the kindred's previously reported ages of 23 and 28 at the respective onset of CSF and PET indicators of fibrillar amyloid-β deposition. It remains to be clarified whether each of these alterations are developmental or reflective of the earliest progressive changes associated with preclinical AD.
Polyethylenimine and chitosan carriers for the delivery of RNA interference effectors (2013)

The use of cationic polymers, especially polyethylenimine and chitosan, for the in vivo delivery of doubled-stranded RNAs is discussed in this review.
Can maitake MD-fraction aid cancer patients? (2002)

Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer.
Connectivity Patterns Revealed by Mapping of Active Inputs on Dendrites of Thalamorecipient Neurons in the Auditory Cortex (2009)

Despite being substantially outnumbered by intracortical inputs on thalamorecipient neurons, thalamocortical projections efficiently deliver acoustic information to the auditory cortex. We hypothesized that thalamic projections may achieve effectiveness by forming synapses at optimal locations on dendritic trees of cortical neurons. Using two-photon calcium imaging in dendritic spines, we constructed maps of active thalamic and intracortical inputs on dendritic trees of thalamorecipient cortical neurons in mouse thalamocortical slices. These maps revealed that thalamic projections synapse preferentially on stubby dendritic spines within 100 microm of the soma, whereas the locations and morphology of spines that receive intracortical projections have a less-defined pattern. Using two-photon photolysis of caged glutamate, we found that activation of stubby dendritic spines located perisomatically generated larger postsynaptic potentials in the soma of thalamorecipient neurons than did activation of remote dendritic spines or spines of other morphological types. These results suggest a novel mechanism of reliability of thalamic projections: the positioning of crucial afferent inputs at optimal synaptic locations.
The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage (2005)

Type X collagen is a reliable marker for new bone formation in articular cartilage. The future clinical application of this collagen in inducing or mediating endochondral ossification is perceived, e.g. the fracture healing of synovial joints and adaptive remodeling of madibular condyle.
Synchrotron radiation computed tomography versus conventional computed tomography for assessment of four types of stent grafts used for endovascular treatment of thoracic and abdominal aortic aneurysms (2018)

This study further confirms the accuracy of high-resolution synchrotron radiation CT in image visualization and size measurement of different aortic stent grafts with measured wire diameters similar to the actual ones, thus allowing for more accurate assessment of stent wire details for endovascular repair of aortic aneurysms.
Generating Nontrivial Melodies for Music as a Service (2017)

We present a hybrid neural network and rule-based system that generates pop music. Music produced by pure rule-based systems often sounds mechanical. Music produced by machine learning sounds better, but still lacks hierarchical temporal structure. We restore temporal hierarchy by augmenting machine learning with a temporal production grammar, which generates the music's overall structure and chord progressions. A compatible melody is then generated by a conditional variational recurrent autoencoder. The autoencoder is trained with eight-measure segments from a corpus of 10,000 MIDI files, each of which has had its melody track and chord progressions identified heuristically. The autoencoder maps melody into a multi-dimensional feature space, conditioned by the underlying chord progression. A melody is then generated by feeding a random sample from that space to the autoencoder's decoder, along with the chord progression generated by the grammar. The autoencoder can make musically plausible variations on an existing melody, suitable for recurring motifs. It can also reharmonize a melody to a new chord progression, keeping the rhythm and contour. The generated music compares favorably with that generated by other academic and commercial software designed for the music-as-a-service industry.
Quantum speedup of Monte Carlo methods (2015)

Monte Carlo methods use random sampling to estimate numerical quantities which are hard to compute deterministically. One important example is the use in statistical physics of rapidly mixing Markov chains to approximately compute partition functions. In this work, we describe a quantum algorithm which can accelerate Monte Carlo methods in a very general setting. The algorithm estimates the expected output value of an arbitrary randomized or quantum subroutine with bounded variance, achieving a near-quadratic speedup over the best possible classical algorithm. Combining the algorithm with the use of quantum walks gives a quantum speedup of the fastest known classical algorithms with rigorous performance bounds for computing partition functions, which use multiple-stage Markov chain Monte Carlo techniques. The quantum algorithm can also be used to estimate the total variation distance between probability distributions efficiently.
Signal processor implementation of variable digital filters (1988)

The implementation of two recently introduced variable digital filter schemes using a TMS320-series digital signal processor is presented. One is a method for updating the coefficients of an FIR (finite-impulse response) filter in a simple manner such that the cutoff frequencies can be controlled through a single parameter. The other is a method for tuning the cutoff frequency of an IIR (infinite-impulse response) filter with one parameter using a series expansion of the low-pass-low-pass frequency transformation. The measured frequency responses compare well with the theory.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Nucleotide sequence of a 1, 3–1, 4-β-glucanase-encoding gene in Bacillus circulans WL-12 (1990)

Journal Article Nucleotide sequence of a 1, 3–1, 4-β-glucanase-encoding gene in Bacillus circulans WL-12 Get access A. Bueno, A. Bueno Instituto de Microbiologia-Bioquimica, Facultad de Biologia, CSIC/Universidad de Salamanca37008 Salamanca, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar C.R.Vazquez de Aldana, C.R.Vazquez de Aldana Instituto de Microbiologia-Bioquimica, Facultad de Biologia, CSIC/Universidad de Salamanca37008 Salamanca, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Correa, J. Correa Instituto de Microbiologia-Bioquimica, Facultad de Biologia, CSIC/Universidad de Salamanca37008 Salamanca, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar F.del Rey F.del Rey Instituto de Microbiologia-Bioquimica, Facultad de Biologia, CSIC/Universidad de Salamanca37008 Salamanca, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 14, 25 July 1990, Page 4248, https://doi.org/10.1093/nar/18.14.4248 Published: 25 July 1990 Article history Received: 15 June 1990 Published: 25 July 1990