gebhart/patrepeval huggingface dataset:
Discovery of multiple hidden allosteric sites by combining Markov state models and experiments (2015)

The discovery of drug-like molecules that bind pockets in proteins that are not present in crystallographic structures yet exert allosteric control over activity has generated great interest in designing pharmaceuticals that exploit allosteric effects. However, there have only been a small number of successes, so the therapeutic potential of these pockets--called hidden allosteric sites--remains unclear. One challenge for assessing their utility is that rational drug design approaches require foreknowledge of the target site, but most hidden allosteric sites are only discovered when a small molecule is found to stabilize them. We present a means of decoupling the identification of hidden allosteric sites from the discovery of drugs that bind them by drawing on new developments in Markov state modeling that provide unprecedented access to microsecond- to millisecond-timescale fluctuations of a protein's structure. Visualizing these fluctuations allows us to identify potential hidden allosteric sites, which we then test via thiol labeling experiments. Application of these methods reveals multiple hidden allosteric sites in an important antibiotic target--TEM-1 β-lactamase. This result supports the hypothesis that there are many as yet undiscovered hidden allosteric sites and suggests our methodology can identify such sites, providing a starting point for future drug design efforts. More generally, our results demonstrate the power of using Markov state models to guide experiments.
Influence of Harmonic Surface Roughness on the Fatigue Life of Elastohydrodynamic Lubricated Contacts (2006)

Abstract In recent years, owing to the increase in transmitted power, increase in temperature, and decrease in viscosity, elastohydrodynamic lubricated (EHL) contact conditions have become extremely severe. Consequently, roughness and surface features become increasingly important when compared with the lubricant film thickness, which can induce wear. Moreover, local pressure variations increasingly cause surface-induced fatigue. Therefore, the understanding of roughness behaviour in EHL contact performance has become important. Three decades ago, a widely used tool to predict contact performance was proposed by Dawson and Tallian. It is based on the central film thickness to composite roughness ( h 3 /σ) ratio. However, engineering fatigue life models require the stress level and the stressed volume to study the contact life reduction, and neither can be extracted directly from the h 3 /σ ratio. This article extends the amplitude reduction analysis. It proposes a new dimensionless parameter including central film thickness, roughness wavelength, and amplitude. It is shown that the pressure fluctuations depend solely on this parameter and that the fatigue life depends mainly on this parameter.
Highly Sensitive Glucose Biosensors Based on Organic Electrochemical Transistors Using Platinum Gate Electrodes Modified with Enzyme and Nanomaterials (2011)

Abstract Organic electrochemical transistors with glucose oxidase‐modified Pt gate electrodes are successfully used as highly sensitive glucose sensors. The gate electrodes are modified with nanomaterials (multi‐wall carbon nanotubes or Pt nanoparticles) for the first time, which results in a dramatic improvement in the sensitivity of the devices. The detection limit of the device modified with Pt nanoparticles on the gate electrode is about 5 nM, which is three orders of magnitude better than a device without the nanoparticles. The improvement of the device performance can be attributed to the excellent electrocatalytic properties of the nanomaterials and more effective immobilization of enzyme on the gate electrodes. Based on the same principle, many other types of enzyme sensors with high sensitivity and low cost are expected to be realized by modifying the gate electrodes of organic electrochemical transistors with specific enzymes and nanomaterials.
Dynamic Signature Verification Using Embedded Sensors (2011)

This paper presents a new method for signature verification using a pen equipped with sensors. Traditional dynamic signature verification methods use digitizing tablets to record data. Here real time data is gathered using sensors embedded in the pen as the person signs. These sensors capture dynamic information of the signing process such as instantaneous acceleration, rotation, and other data. After processing raw data, classification is made using a combination of techniques such as dynamic time warping and hidden Markov models with Gaussian mixtures. Along with global feature comparison this method yields low false acceptance rate and false rejection rate. Details of a prototype system and performance on human subjects are also presented.
Antibody Aggregation: Insights from Sequence and Structure (2016)

Monoclonal antibodies (mAbs) are the fastest-growing biological therapeutics with important applications ranging from cancers, autoimmunity diseases and metabolic disorders to emerging infectious diseases. Aggregation of mAbs continues to be a major problem in their developability. Antibody aggregation could be triggered by partial unfolding of its domains, leading to monomer-monomer association followed by nucleation and growth. Although the aggregation propensities of antibodies and antibody-based proteins can be affected by the external experimental conditions, they are strongly dependent on the intrinsic antibody properties as determined by their sequences and structures. In this review, we describe how the unfolding and aggregation susceptibilities of IgG could be related to their cognate sequences and structures. The impact of antibody domain structures on thermostability and aggregation propensities, and effective strategies to reduce aggregation are discussed. Finally, the aggregation of antibody-drug conjugates (ADCs) as related to their sequence/structure, linker payload, conjugation chemistry and drug-antibody ratio (DAR) is reviewed.
Microfabricated hollow microneedle array using ICP etcher (2006)

10.1088/1742-6596/34/1/187
Carbon‐flux distribution in the central metabolic pathways of <i>Corynebacterium glutamicum</i> during growth on fructose (1998)

Growth of Corynebacterium glutamicum on fructose was significantly less than that obtained on glucose, despite similar rates of substrate uptake. This was in part due to the production of overflow metabolites (dihydroxyacetone and lactate) but also to the increased production of CO2 during growth on fructose. These differences in carbon-metabolite accumulation are indicative of a different pattern of carbon-flux distribution through the central metabolic pathways. Growth on glucose has been previously shown to involve a high flux (> 50% of total glucose consumption) via the pentose pathway to generate anabolic reducing equivalents. NMR analysis of carbon-isotope distribution patterns of the glutamate pool after growth on 1-13C- or 6-13C-enriched fructose indicates that the contribution of the pentose pathway is significantly diminished during exponential growth on fructose with glycolysis being the predominant pathway (80% of total fructose consumption). The increased flux through glycolysis during growth on fructose is associated with an increased NADH/NAD+ ratio susceptible to inhibit both glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenase, and provoking the overflow of metabolites derived from the substrates of these two enzymes. The biomass yield observed experimentally is higher than can be estimated from the apparent quantity of NADPH associated with the pentose pathway and the flux through isocitrate dehydrogenase, suggesting an additional reaction yielding NADPH. This may involve a modified tricarboxylic acid cycle involving malic enzyme, expressed to significantly higher levels during growth on fructose than on glucose, and a pyruvate carboxylating anaplerotic enzyme.
EMLA: a new topical anesthetic. (1990)

Eutectic Mixture of Local Anesthetics (EMLA) containing 5% lidocaine and prilocaine in a cream was found to give effective topical analgesia in normal and diseased skin, making it useful for superficial surgery and various other clinical procedures. To be effective, an adequate amount must be applied under occlusion and at the right time before the intervention.
Biochemical and Genetic Characterization of an FK506-Sensitive Peptidyl Prolyl<i>cis-trans</i>Isomerase from a Thermophilic Archaeon,<i>Methanococcus thermolithotrophicus</i> (1998)

ABSTRACT A peptidyl prolyl cis-trans isomerase (PPIase) was purified from a thermophilic methanogen, Methanococcus thermolithotrophicus . The PPIase activity was inhibited by FK506 but not by cyclosporine. The molecular mass of the purified enzyme was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 42 kDa by gel filtration. The enzyme was thermostable, with the half-lives of its activity at 90 and 100°C being 90 and 30 min, respectively. The catalytic efficiencies ( k cat / K m ) measured at 15°C for the peptidyl substrates, N -succinyl-Ala-Leu-Pro-Phe- p -nitroanilide and N -succinyl-Ala-Ala-Pro-Phe- p -nitroanilide, were 0.35 and 0.20 μM −1 s −1 , respectively, in chymotrypsin-coupled assays. The purified enzyme was sensitive to FK506 and therefore was called MTFK ( M. thermolithotrophicus FK506-binding protein). The MTFK gene (462 bp) was cloned from an M. thermolithotrophicus genomic library. The comparison of the amino acid sequence of MTFK with those of other FK506-binding PPIases revealed that MTFK has a 13-amino-acid insertion in the N-terminal region that is unique to thermophilic archaea. The relationship between the thermostable nature of MTFK and its structure is discussed.
Monitoring of a Calcination Reaction of High Reflective Green-Black (HRGB) Pigments by Using Near-Infrared Electronic Spectroscopy: Calcination Temperature-Dependent Crystal Structural Changes of Their Components and Calibration of the Extent of the Reaction (2012)

This paper demonstrates the potential of near-infrared (NIR) electronic spectroscopy in nondestructive monitoring of a chemical reaction of inorganic functional material. For this purpose NIR spectra in the 12,000-4000 cm(-1) region were measured for high reflective green-black (HRGB) pigments (Co(0.5)Mg(0.5)Fe(0.5)Al(1.5)O(4)) calcined at 1000, 1100, and 1200 °C and pigments with the same components as HRGB but calcined at different temperatures (500-900 °C) (hereafter, called "Pigments A") . NIR spectra of their components such as Co(3)O(4), MgO, Fe(2)O(3), and Al(2)O(3) were also measured. The NIR spectra of Pigments A show two major broad bands. One arises from a (4)A(2)→(4)T(1) (T(h)) d-d transition of Co(II) in the 9000-6000 cm(-1) region. The other band in the 12,000-9000 cm(-1) region is assigned to a foot of the charge-transfer (CT) band of Fe(2)O(3). The Co(II) band contains three component bands that are characteristic of a spinel structure. A shoulder arising from (A(1-x)B(x))(Th)(A(x)B(2-x))(Oh)O(4) (A≡Co, Mg, B≡Fe, Al; inverse spinel structure) emerges near 5900 cm(-1) in the spectra of Pigments A calcined in the temperature range of 700-900 °C, indicating that the Pigments A calcined in this temperature range assume an inverse spinel structure. When the calcination temperature is above 1000 °C, the final product, HRGB, is produced. This is confirmed from the fact that HRGB shows peaks characteristic of a spinel structure that have different wavenumbers from those of the corresponding peaks of Pigments A. Wide-angle X-ray diffraction (WAXD) patterns were also measured for HRGB, Pigments A, and their components. Based on the NIR and WAXD data we investigated calcination-temperature-dependent crystal structural changes of the components. We also developed partial least squares (PLS) calibration models for the 9000-6000 cm(-1) region of the NIR spectra of HRGB and Pigments A. The score plot of latent variable (LV) 2 of the calibration model for calcination temperature demonstrates clearly the existence of an intermediate of the calcination reaction, which may be (A(1-x)B(x))(Th)(A(x)B(2-x))(Oh)O(4) (A≡Co, Mg, B≡Fe, Al).
γ‐Synuclein and the progression of cancer (2007)

The synucleins are a small, soluble, highly conserved group of neuronal proteins that have been implicated in both neurodegenerative diseases and cancer. The synuclein family consists of alpha-, beta-, and gamma-synucleins (gamma-syn). They are a natively unfolded group of proteins that share sequence homologies and structural properties. So far, the biological functions of the synucleins are still unclear, but their involvement in neurodegenerative diseases and cancer may provide insights into the pathological processes that result from these two groups of debilitating diseases, and present the possibility to use them as potential targets for early diagnosis and treatment. Recently, elevated levels of gamma-syn proteins have been detected in various types of cancer, especially in advanced stages of the disease. Furthermore, studies to date indicate that overexpression of gamma-syn compromises normal mitotic checkpoint controls, resulting in multinucleation as well as faster cell growth. Gamma-syn has also been shown to promote invasion and metastasis in in vitro assays as well as in animal models. Overexpression of gamma-syn also interferes with drug-induced apoptotic responses. These observations raise questions about the involvement of gamma-syn in the process of tumorigenesis and metastasis, and efforts have already been made to use gamma-syn as a marker for assessing breast cancer progression. This review will discuss the involvement of gamma-syn in cancer progression, metastasis and its potential as a marker.
The Lessons of History (2002)

A short time ago, I acted as the narrator in a performance of Aaron Copland's moving piece "Lincoln Portrait." The words I read included those delivered by President Abraham Lincoln to the Congress on December 1, 1862, in the midst of the Civil War. The subject was slavery. Lincoln's famous speech concluded: "Fellow-citizens, we can not escape history." On this important occasion honoring the life and legacy of one of the great figures of our period, the late Judge A. Leon Higginbotham, Jr. let me say that my special friend and esteemed colleague also knew well the value of looking back to move forward.
Revisiting Perceptually Optimized Color Mapping for High-Dimensional Data Analysis (2014)

Color is one of the most effective visual variables since it can be combined with other mappings and encodeinformation without using any additional space on the display. An important example where expressing additionalvisual dimensions is direly needed is the analysis of high-dimensional data. The property of perceptual linearity isdesirable in this application, because the user intuitively perceives clusters and relations among multi-dimensionaldata points. Many approaches use two-dimensional colormaps in their analysis, which are typically created byinterpolating in RGB, HSV or CIELAB color spaces. These approaches share the problem that the resulting colorsare either saturated and discriminative but not perceptual linear or vice versa. A solution that combines bothadvantages has been previously introduced by Kaski et al.; yet, this method is to date underutilized in InformationVisualization according to our literature analysis. The method maps high-dimensional data points into the CIELABcolor space by maintaining the relative perceived distances of data points and color discrimination. In this paper,we generalize and extend the method of Kaski et al. to provide perceptual uniform color mapping for visual analysisof high-dimensional data. Further, we evaluate the method and provide guidelines for different analysis tasks.
Lathyrism: a neurotoxic disease. (1984)

Lathyrism, one of the oldest neurotoxic diseases known to Man, results from excessive consumption of the chickling pea, Lathyrus sativus, and certain related species. Once prevalent throughout Europe, N. Africa, Middle East and parts of the Far East, the disease is presently restricted to India, Bangladesh and Ethiopia. Lathyrism is a form of irreversible, non-progressive spastic paraparesis associated with poorly understood degenerative changes in spinal cord. Domestic animals, notably the horse, also develop hindlimb paralysis after prolonged feeding on lathyrus fodder. Experimental animal models of lathyrism have been reported but none has been satisfactorily investigated, and concurrence between these experimental diseases and the human condition is unproven. The culpable agent in lathyrus species that precipitates paralysis also is unknown. Current attention is focused on the glutamate analog, beta-(N)-oxalyl-amino-L-alanine acid (BOAA). While this compound is present in those lathyrus species that induce spastic paraparesis and, in large doses, reportedly causes neuropathological changes similar to glutamate neurotoxicity, there is little to compare these neuropathological changes with those found in human lathyrism. Chronic primate feeding studies utilizing BOAA need to be carried out to determine whether this agent is responsible for human lathyrism. Some species of lathyrus, notably Lathyrus odoratus, are unable to induce human lathyrism but contain a compound, beta-aminopropionitrile (BAPN), that induces pathological changes in bone ("osteolathyrism") and blood vessels ("angiolathyrism") of experimental animals without damaging the nervous system. However, related compounds, dimethylaminopropionitrile (DMAPN) and beta, beta'-iminodipropionitrile (IDPN), are chronic neurotoxins in humans and animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Trichothecium cinnamomeum, an Earlier Name for the Thermophilic Hyphomycete Malbranchea sulfurea (1987)

"Trichothecium Cinnamomeum, An Earlier Name for the Thermophilic Hyphomycete Malbranchea Sulfurea." Mycologia, 79(1), pp. 142–143Key Words: Trichothecium cinnamomeumMalbranchea sulfureaMalbranchea cinnamomeathermophile
Granular cell myoblastoma (1970)

Abstract Eleven cases of granular cell myoblastoma are reported. Eight cases were symptomatic and consist of clinical material. None of these were diagnosed preoperatively. The other three cases are incidental findings from routine autopsies. All tumors are benign clinically and histologically. The treatment of choice is local wide excision. It is worthwhile to indicate that this tumor can occur in combination with other malignant tumors (Table II), but we do not believe that there is any correlation.
Parametrization of PostScript fonts through METAFONT - an alternative to Adobe Multiple Master fonts (1993)

In this paper we present a new method of parametrizing PostScript fonts in order to create font families. By changing parameter values one can obtain different weights, condensed or expanded versions, small caps as well as optically scaled fonts. The tool used to parametrize PostScript fonts is D. E. Knuth&apos;s METAFONT program. Instead of designing a font from scratch, METAFONT is used as an extrapolator of existing PostScript fonts: out of the information contained in them we build a meta-font; for every choice of parameter values, special versions of METAFONT allow us to return to PostScript and produce a new PostScript font.
GD2-targeted chimeric antigen receptor T cells prevent metastasis formation by elimination of breast cancer stem-like cells (2019)

Expression of the disialoganglioside GD2 has been identified as a marker antigen associated with a breast cancer stem-like cell (BCSC) phenotype. Here, we report on the evaluation of GD2 as a BCSC-specific target antigen for immunotherapy. GD2 expression was confirmed at variable degree in a set of breast cancer cell lines, predominantly in triple-negative breast cancer (TNBC). To target GD2, we have generated novel anti-GD2 chimeric antigen receptors (GD2-CAR), based on single-chain variable fragments (scFv) derived from the monoclonal antibody (mAb) ch14.18, also known as dinutuximab beta. Expressed on T cells, GD2-CARs mediated specific GD2-dependent T-cell activation and target cell lysis. In contrast to previously described GD2-CARs, no signs of exhaustion by tonic signaling were found. Importantly, application of GD2-CAR expressing T cells (GD2-CAR-T) in an orthotopic xenograft model of TNBC (MDA-MB-231) halted local tumor progression and completely prevented lung metastasis formation. In line with the BCSC model, GD2 expression was only found in a subpopulation (4-6%) of MDA-MB-231 cells before injection. Significant expansion of GD2-CAR-T in tumor-bearing mice as well as T-cell infiltrates in the primary tumor and the lungs were found, indicating site-specific activation of GD2-CAR-T. Our data strongly support previous findings of GD2 as a BCSC-associated antigen. GD2-targeted immunotherapies have been extensively studied in human. In conclusion, GD2-CAR-T should be considered a promising novel approach for GD2-positive breast cancer, especially to eliminate disseminated tumor cells and prevent metastasis formation.
Meta-gui-builders (2008)

Nowadays, there is a growing demand to design user interfaces that run on many devices. However, existing multi-device design approaches are not suitable for domain experts, whose input can be invaluable to come to a suitable user interface for a specific domain. Existing techniques often require the manipulation of high-level models and transformations which are difficult to interpret and predict by a domain expert without a technical background. We present Meta-GUI-Builders, a new generation of graphical user interface builder tools that allows domain experts to create multi-device GUI designs themselves. These tools automatically adapt their workspace to a specific domain by encapsulating domain-specific elements in the designer's tool palette. Engaging domain experts in a multi-device design approach is a first step towards creating aesthetic user interfaces that can be deployed on many devices, a combination that is hard to achieve with previous approaches.
Failure of isotretinoin and interferon-alpha combination therapy for HPV-linked severe vulvar dysplasia. A report of two cases. (1998)

These data demonstrate the ineffectiveness of the combined regimen of IFN-alpha and 13 cRA with this schedule for a period of six months in recurrent and chronic VIN 3.
Space and phase resolved plasma parameters in an industrial dual-frequency capacitively coupled radio-frequency discharge (2007)

TEST 02 - Elsevier's Scopus, the largest abstract and citation database of peer-reviewed literature. Search and access research from the science, technology, medicine, social sciences and arts and humanities fields.
Low-inductance module construction for high speed, high-current IGBT module suitable for electric vehicle application (2002)

A low-inductance IGBT (insulated-gate bipolar transistor) module construction is presented. Sufficiently low stray inductance in the module has been realized by adopting a multilayered DBC (direct bond copper) substrate, optimally designed terminals, and the optimum arrangement of terminals. This module construction has made possible high-speed and high-current switching operation with low overshoot voltage. A 600-V/400-A half-bridge circuit is constructed with about 80% of the package size for a conventional module. This module is particularly suitable for 40-50 kW electric vehicle applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>