gebhart/patrepeval huggingface dataset:
Phosphorylation but Not Oligomerization Drives the Accumulation of Tau with Nucleoporin Nup98 (2022)

Tau is a neuronal protein that stabilizes axonal microtubules (MTs) in the central nervous system. In Alzheimer's disease (AD) and other tauopathies, phosphorylated Tau accumulates in intracellular aggregates, a pathological hallmark of these diseases. However, the chronological order of pathological changes in Tau prior to its cytosolic aggregation remains unresolved. These include its phosphorylation and detachment from MTs, mislocalization into the somatodendritic compartment, and oligomerization in the cytosol. Recently, we showed that Tau can interact with phenylalanine-glycine (FG)-rich nucleoporins (Nups), including Nup98, that form a diffusion barrier inside nuclear pore complexes (NPCs), leading to defects in nucleocytoplasmic transport. Here, we used surface plasmon resonance (SPR) and bio-layer interferometry (BLI) to investigate the molecular details of Tau:Nup98 interactions and determined how Tau phosphorylation and oligomerization impact the interactions. Importantly, phosphorylation, but not acetylation, strongly facilitates the accumulation of Tau with Nup98. Oligomerization, however, seems to inhibit Tau:Nup98 interactions, suggesting that Tau-FG Nup interactions occur prior to oligomerization. Overall, these results provide fundamental insights into the molecular mechanisms of Tau-FG Nup interactions within NPCs, which might explain how stress-and disease-associated posttranslational modifications (PTMs) may lead to Tau-induced nucleocytoplasmic transport (NCT) failure. Intervention strategies that could rescue Tau-induced NCT failure in AD and tauopathies will be further discussed.
Highway Design Handbook for Older Drivers and Pedestrians (2001)

This project updated, revised, and expanded the scope of the Driver Highway Design published by the Federal Highway Administration (FHWA) in 1998. The resulting document incorporates new research findings and technical developments; extensive feedback from State, county, and municipal engineers who reviewed and applied recommendations from the earlier version of the Handbook; and recommendations with supporting background material for aspects of modern roundabouts and highway-rail grade crossings, two elements that were not covered in the 1998 publication. Recommendations geared to use of highway facilities by pedestrians also receive greater emphasis. Guidance on how and when to implement the included recommendations has been added, as well as codes that indicate at a glance the relationship of each recommendation with standard design manuals, including the Manual on Uniform Traffic Control Devices and the AASHTO Green Book. Development of the updated Handbook was complemented in this project by a technology transfer initiative to make practitioners aware of the Handbook and assist in applying its recommendations. This included the development of a condensed document, Guidelines and Recommendations to Accommodate Older Drivers and Pedestrians (FHWA-RD-01-051), plus printed and electronic materials supporting the conduct of practitioner workshops throughout the United States in the 1999-2001 period. All research products developed under this contract are designed to provide practical guidance to engineers to accommodate the needs and functional limitations of an aging population of road users. Included recommendations are directed toward new construction, reconstruction, scheduled maintenance, and spot treatments to ameliorate demonstrated safety problems, emphasizing countermeasures with modest additional cost during installation and the potential for a cost-savings over the life cycle.
Prevention of Undesirable Isomerization during Olefin Metathesis (2005)

1,4-Benzoquinones have been found to prevent olefin isomerization of a number of allylic ethers and long-chain aliphatic alkenes during ruthenium-catalyzed olefin metathesis reactions. Electron-deficient benzoquinones are the most effective additives for the prevention of olefin migration. This mild, inexpensive, and effective method to block olefin isomerization increases the synthetic utility of olefin metathesis via improvement of overall product yield and purity.
Determining the minimum embedding dimension of nonlinear time series based on prediction method (2004)

Determining the embedding dimension of nonlinear time series plays an important role in the reconstruction of nonlinear dynamics. The paper first summarizes the current methods for determining the embedding dimension. Then, inspired by the fact that the optimum modelling dimension of nonlinear autoregressive (NAR) prediction model can characterize the embedding feature of the dynamics, the paper presents a new idea that the optimum modelling dimension of the NAR model can be taken as the minimum embedding dimension. Some validation examples and results are given and the present method shows its advantage for short data series.
ChemInform Abstract: ALPHA,BETA‐EPOXY‐SULFOXIDE UND ‐SULFONE, THERMISCHE UND SAURE UMALGERUNGSRK. (1970)

Abstract In Gegenwart von tert.‐Butylat erhält man aus Chlormethyl‐sulfoxiden wie (I) mit den Oxoverbindungen (II) die Epoxy‐sulfoxide (III).
Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes. (1999)

Although tightly linked, the TCR alpha and delta genes are expressed specifically in T lymphocytes, whereas the Dad1 gene is ubiquitously expressed. Between TCR alpha and Dad1 are eight DNase I hypersensitive sites (HS). HS1 colocalizes with the TCR alpha enhancer (Ealpha) and is T cell-specific; HS2, -3, -4, -5, and -6 map downstream of HS1 and are tissue-nonspecific. The region spanning HS2-6 was reported to display chromatin-opening activity and to confer copy number-dependent and integration site-independent transgene expression in transgenic mice. Here, we demonstrate that HS2-6 also displays enhancer-blocking activity, as it can block an enhancer from activating a promoter when located between the two in a chromatin-integrated context, and can do so without repressing either the enhancer or the promoter. Multiple enhancer-blocking elements are arrayed across HS2-6. We show that HS2-6 by itself does not activate transcription in chromatin context, but can synergize with an enhancer when located upstream of an enhancer and promoter. We propose that HS2-6 primarily functions as an insulator or boundary element that may be critical for the autonomous regulation of the TCR alpha and Dad1 genes.
Engineering rich internet applications with a model-driven approach (2010)

Rich Internet Applications (RIAs) have introduced powerful novel functionalities into the Web architecture, borrowed from client-server and desktop applications. The resulting platforms allow designers to improve the user's experience, by exploiting client-side data and computation, bidirectional client-server communication, synchronous and asynchronous events, and rich interface widgets. However, the rapid evolution of RIA technologies challenges the Model-Driven Development methodologies that have been successfully applied in the past decade to traditional Web solutions. This paper illustrates an evolutionary approach for incorporating a wealth of RIA features into an existing Web engineering methodology and notation. The experience demonstrates that it is possible to model RIA application requirements at a high-level using a platform-independent notation, and generate the client-side and server-side code automatically. The resulting approach is evaluated in terms of expressive power, ease of use, and implementability.
Functional protection of dystrophic mouse (mdx) muscles after adenovirus-mediated transfer of a dystrophin minigene. (1996)

Fast skeletal muscles of mdx (X chromosome-linked muscular dystrophy) mice were injected after birth with a recombinant adenovirus containing a minidys- trophin gene, a 6.3-kbp cDNA coding for the N- and C-terminal ends of dystrophin. Adult muscles were challenged by forced lengthening during tetanic contractions. Stretch-induced mechanical and histological damages were much reduced in injected muscles, in direct proportion of the Miniber of fibers expressing minidystrophin. Damaged fibers were preferentially found among minidystrophin-negative regions. Minidystrostrophin confers an important functional and structural protection of limb muscles against high mechanical stress, even after a partial somatic gene transfer.
Regulation of Glutamate Dehydrogenases in nit-2 and am Mutants of Neurospora crassa (1979)

The regulation of the glutamate dehydrogenases was investigated in wild-type Neurospora crassa and two classes of mutants altered in the assimilation of inorganic nitrogen, as either nitrate or ammonium. In the wild-type strain, a high nutrient carbon concentration increased the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-glutamate dehydrogenase and decreased the activity of reduced nicotinamide adenine dinucleotide (NADH)-glutamate dehydrogenase. A high nutrient nitrogen concentration had the opposite effect, increasing NADH-glutamate dehydrogenase and decreasing NADPH-glutamate dehydrogenase. The nit-2 mutants, defective in many nitrogen-utilizing enzymes and transport systems, exhibited low enzyme activities after growth on a high sucrose concentration: NADPH-glutamate dehydrogenase activity was reduced 4-fold on NH 4 Cl medium, and NADH-glutamate dehydrogenase, 20-fold on urea medium. Unlike the other affected enzymes of nit-2 , which are present only in basal levels, the NADH-glutamate dehydrogenase activity was found to be moderately enhanced when cells were grown on a low carbon concentration. This finding suggests that the control of this enzyme in nit-2 is hypersensitive to catabolite repression. The am mutants, which lack NADPH-glutamate dehydrogenase activity, possessed basal levels of NADH-glutamate dehydrogenase activity after growth on urea or l -aspartic acid media, like the wild-type strain, and possessed moderate levels (although three- to fourfold lower than the wild-type strain) on l -asparagine medium or l -aspartic acid medium containing NH 4 Cl. These regulatory patterns are identical to those of the nit-2 mutants. Thus, the two classes of mutants exhibit a common defect in NADH-glutamate dehydrogenase regulation. Double mutants of nit-2 and am had lower NADH-glutamate dehydrogenase activities than either parent. A carbon metabolite is proposed to be the repressor of NADH-glutamate dehydrogenase in N. crassa .
Experimenting with TCPA/TCG Hardware, Or: How I Learned to Stop Worrying and Love The Bear (2003)

Abstract. Over the last few years, our group has been working on applications of secure coprocessors—but has been frustrated by the limited computational environment and high expense of such devices. Over the last few years, the TCPA (now TCG) has produced a specification for a trusted platform module (TPM)—a small hardware addition intended to improve the overall security of a larger machine (and tied up with a still-murky vision of Windows-based trusted computing). Some commodity desktops now come up with these TPMs. Consequently, we began an experiment to see if (in the absence of a Non-Disclosure Agreement) we could use this hardware to transform a desktop Linux machine into a virtual secure coprocessor: more powerful but less secure than higher-end devices. This experiment has several purposes: to provide a new platform for secure coprocessor applications, to see how well the TCPA/TCG approach works, and (by working in open source) to provide a platform for the broader community to experiment with alternative architectures in the contentious area of trusted computing. This paper reports what we have learned so far: the approach is feasible, but effective deployment requires a more thorough look at OS security. 1
Nutritional intervention by a novel slow-release niacin formulation beneficially alters the gut microbiome and promotes systemic metabolic effects in humans (2017)

Obesity and type 2 diabetes have been linked to abnormalities in the gut microbiota. In animal models, administration of Niacin (Vitamin B3), which is a major metabolite of cellular tryptophan metabolism, beneficially affects the microbiome-host axis. By measuring Niacin levels in n = 511 humans we found reduced concentrations in obese and type 2 diabetic subjects, suggesting Niacin administration to be beneficial also in humans. However, orally administration of Niacin in humans rapidly results in systemic resorption in the upper gastro-intestinal (GI) tract leading to a facial flush. Therefore, in the present study we developed a novel microencapsulation procedure using food grade ingredients in order to prevent resorption of Niacin in the upper GI tract and enabling a sufficient release of the nutrient in the ileo-colonic region. In a first human intervention trial we were able to show that the microencapsulation procedure efficiently prevents systemic resorption and that no severe side effects and no flush occur. Fecal 16sDNA microbiome sequencing revealed significant changes in the Bacteroidetes in response to orally administered microencapsulated Niacin. Of importance, microencapsulated Niacin but not naïve Niacin resulted in beneficial systemic metabolic effects, suggesting an indirect mechanism via the microbiome rather than a direct effect of the nutrient itself. In summary, our data suggest that a targeted microbiome intervention using advanced food technology is able to induce beneficial systemic metabolic effects in humans. Thus, food enriched with microencapsulated Niacin might be a novel prevention/treatment option for obesity and type 2 diabetes in the future.
III–V Multiple-Gate Field-Effect Transistors With High-Mobility $\hbox{In}_{0.7}\hbox{Ga}_{0.3}\hbox{As}$ Channel and Epi-Controlled Retrograde-Doped Fin (2011)

We report an In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.7</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.3</sub> As n-channel multiple-gate field-effect transistor (MuGFET), featuring a lightly doped high-mobility channel with 70% indium and an epi-controlled retrograde-doped fin structure to suppress short-channel effects (SCEs). The retrograde well effectively reduces subsurface punch-through in the bulk MuGFET structure. The multiple-gate structure achieves good electrostatic control of the channel potential and SCEs in the In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.7</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.3</sub> As n-MuGFETs as compared with planar In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.7</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.3</sub> As MOSFETs. The In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.7</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.3</sub> As n-MuGFET with 130-nm channel length demonstrates a drain-induced barrier lowering of 135 mV/V and a drive current exceeding 840 μA/μm at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</sub> = 1.5 V and V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GS</sub> - V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> = 3 V.
Oxetanocin—Oxetanose Chemistry: Lewis Acid Promoted Glycosidations of the D-Erythrooxetanose Derivatives (1992)

Abstract Upon treatment of 1-O-acetyl-D-erythrooxetanoses (17a,b and 26) with trimethylsilyl N-benzoyladenine or allyltrimethylsilane in the presence of SnCl4, the ring expanded products (18, 19 and 29) or the acyclic compounds (27 and 28) were obtained. The reaction mechanism involving a novel ring opening process is discussed.
Identifying refactoring sequences for improving software maintainability (2012)

Refactoring is a well-known technique that preserves software behaviors and improves its bad structures or bad smells. In most cases, more than one bad smell is found in a program. Consequently, developers frequently apply refactorings more than once. Applying appropriate refactoring sequences, an ordered list of refactorings, developers can remove bad smells as well as reduce improvement time and produce highly maintainable software. According to our 2011 survey, developers consider four main criteria to select an optimal refactoring sequence: 1) the number of removed bad smells, 2) maintainability, 3) the size of refactoring sequence and 4) the number of modified program elements. A refactoring sequence that satisfies these four criteria produces code without bad smells, with higher maintainability, using the least improvement effort and time, and providing more traceability. Some existing works suggest a list of refactorings without ordering, and others suggest refactoring sequences. However, these works do not consider the four criteria discussed earlier. Therefore, our research proposes an approach to identify an optimal refactoring sequence that meets these criteria. In addition, it is expected that the findings will reduce maintenance time and cost, increase maintainability and enhance software quality.
Characterization of single and multiple scatter from matter and activity distributions outside the FOV in PET (2005)

Operation of PET in 3D mode, without internal septa results in increased sensitivity but at the cost of increased scatter fraction. Significant amounts of scattered events in 3D PET either originate from activity outside the FOV (OFOV) or scatter from matter outside the FOV, complicating scatter correction methods. We performed 3D PET simulations with scanner geometry based on the GE Advance with several phantom geometries designed to characterize all scatter with particular attention to that from outside the FOV. Scatter from OFOV matter was deduced by performing simulations with matter and activity within the FOV only (short phantom). Studies were repeated with phantoms with identical characteristics inside the FOV but with additional OFOV material (long phantom) but no activity outside the FOV. The incremental effect of OFOV activity was then determined by repeating the long phantom studies with additional activity. Scatter was also classified as single or multiple. In summary, the data allows extraction of yields from unscattered and all types of scattered events. The effect of source position, both within and external to the FOV, on scatter was determined by performing a series of simulations with point sources and techniques similar to those described above. The effect of energy discriminator setting (with BGO detectors) was also studied and data sets were generated for five settings from 300 to 425 keV. Using a Zubal phantom with the lungs and heart in the FOV and the abdomen outside the FOV and with a 300 keV discriminator, we find a total scatter fraction of 57%. Of the total scatter, 7.4% comes from OFOV matter and 24% from OFOV activity. If the discriminator is increased to 425 keV the scatter fraction drops to 36%. OFOV scatter, particularly from OFOV activity, becomes relatively less important with the OFOV matter contribution dropping to 5.3% and OFOV activity contribution to 17%. Additionally, the spatial distributions of scatter from external matter and external activity were found to be different.
Breath acetone analyzer: diagnostic tool to monitor dietary fat loss (1993)

Acetone, a metabolite of fat catabolism, is produced in excessive amounts in subjects on restricted-calorie weight-loss programs. Breath acetone measurements are useful as a motivational tool during dieting and for monitoring the effectiveness of weight-loss programs. We have developed a simple, easy-to-read method that quantifies the amount of acetone in a defined volume of exhaled breath after trapping the sample in a gas-analyzer column. The concentration of acetone, as measured by the length of a blue color zone in the analyzer column, correlates with results obtained by gas chromatography. Using the breath acetone analyzer to quantify breath acetone concentrations of dieting subjects, we established a correlation between breath acetone concentration and rate of fat loss (slope 52.2 nmol/L per gram per day, intercept 15.3 nmol/L, n = 78, r = 0.81). We also discussed the possibility of using breath acetone in diabetes management.
Two-Dimensional Coupling in Tuned Coherent Hexagonal Vertical Cavity Laser Arrays (2019)

A 6-element hexagonal vertical-cavity surface-emitting laser array is resonantly tuned to coherence. The far-field profile is narrowed in two-dimensions, with a Full Width at Half Maximum of 2° compared to a single-emitter with 10° FWHM. Multiple coherent outputs are possible dependent on the tuned bias condition, making this technology promising for two-dimensional mode engineering.
Predictive Models for Human Organ Toxicity Based on In Vitro Bioactivity Data and Chemical Structure (2020)

Traditional toxicity testing reliant on animal models is costly and low throughput, posing a significant challenge with the increasing numbers of chemicals that humans are exposed to in the environment. The purpose of this investigation was to build optimal prediction models for various human <i>in vivo</i>/organ-level toxicity end points (extracted from ChemIDPlus) using chemical structure and Tox21 <i>in vitro</i> quantitative high-throughput screening (qHTS) bioactivity assay data. Several supervised machine learning algorithms were applied to model 14 human toxicity end points pertaining to vascular, kidney, ureter and bladder, and liver organ systems. Three metrics were used to evaluate model performance: area under the receiver operating characteristic curve (AUC-ROC), balanced accuracy (BA), and Matthews correlation coefficient (MCC). The top four models, with AUC-ROC values >0.8, were derived for endocrine (0.90 ± 0.00), musculoskeletal (0.88 ± 0.02), peripheral nerve and sensation (0.85 ± 0.01), and brain and coverings (0.83 ± 0.02) toxicities, whereas the best model AUC-ROC values were >0.7 for the remaining 10 toxicities. Model performance was found to be dependent on the specific data set, model type, and feature selection method used. In addition, chemical structure and assay data showed different levels of contribution to the prediction of different toxicity end points. Although <i>in vitro</i> assay data, when combined with chemical structure, slightly improved the predictive accuracy for most end points (11 out of 14), a noteworthy finding was the near equal success of the structure-only models, which do not require Tox21 qHTS screening data, and the relatively poor performance of assay-only models. Thus, the top-performing structure-only models from this study could be applied for hazard screening of large sets of chemicals for potential human toxicity, whereas the largest assay contributions to models (i.e., cellular targets) could be used, along with the top-contributing structural features, to provide insight into toxicity mechanisms.