gebhart/patrepeval huggingface dataset:
Development of an attenuated smallpox vaccine candidate: The KVAC103 strain (2021)

Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox has emerged as the most threatening bio-terrorism agent; as the first- and second-generation smallpox vaccines have been controversial and have caused severe adverse reactions, new demands for safe smallpox vaccines have been raised and some attenuated smallpox vaccines have been developed. We have developed a cell culture-based highly attenuated third-generation smallpox vaccine candidate KVAC103 strain by 103 serial passages of the Lancy-Vaxina strain derived from the Lister in Vero cells. Several clones were selected, taking into consideration their shape, size, and growth rate in mammalian cells. The clones were then inoculated intracerebrally in suckling mice to test for neurovirulence by observing survival. Protective immune responses in adult mice were examined by measuring the levels of neutralization antibodies and IFN-γ expression. Among several clones, clone 7 was considered the best alternative candidate because there was no mortality in suckling mice against a lethal challenge. In addition, enhanced neutralizing antibodies and T-cell mediated IFN-γ production were observed in clone 7-immunized mice. Clone 7 was named "KVAC103" and was used for the skin toxicity test and full-genome analysis. KVAC103-inoculated rabbits showed reduced skin lesions compared to those inoculated with the Lister strain, Lancy-Vaxina. A whole genome analysis of KVAC103 revealed two major deleted regions that might contribute to the reduced virulence of KVAC103 compared to the Lister strain. Phylogenetic inference supported the close relationship with the Lister strain. Collectively, our data demonstrate that KVAC103 holds promise for use as a third-generation smallpox vaccine strain due to its enhanced safety and efficacy.
Electrospray Device for Coupling Microscale Separations and Other Miniaturized Devices with Electrospray Mass Spectrometry (2001)

A miniaturized ion sprayer device is described which is suitable for coupling with chip-based analytical separation devices, multiwell plates, or surfaces containing residues of prepared samples. Two versions of a similar device are described. A "microsprayer" device suitable for coupling to the terminal edge of a capillary electrophoresis (CE) chip is constructed from modified 1/16-in. HPLC fittings. This microsprayer employs a free-standing liquid junction formed via continuous delivery of a flow (2-6 microL/min) of suitable solvent which carries the CE effluent through a pneumatically assisted electrospray (ion spray) needle positioned in front of an atmospheric pressure ionization (API) mass spectrometer. A related but larger "minisprayer" device is also described which employs the same features as the microsprayer, but with an extended sampling capillary tube which can reach into the depths of 96-, 384-, and 1536-multiwell plates containing either sample solutions or dried sample residues. The minisprayer may be positioned in front of an API ion sampling orifice and the multiwell plate positioned stepwise from sample to sample for analysis of trace samples contained in the wells. The resulting infusion-ion spray mass spectrometric analyses can provide sequential analysis of previously prepared biological samples containing small drug compounds, proteins, and related compounds. This same device is also shown to be useful for sampling from a surface containing trace level compounds of biological interest. Results are shown that demonstrate microscale separations and selected ion monitoring (SIM) capillary electrophoresis/mass spectrometry (CE/MS) detection of berberine and palmatine using the microsprayer. SIM ion spray determination of a 2 ng/microL solution of berberine contained as a dry residue in the bottom of a 384-well plate as well as full-scan electrospray mass spectra for low-picomole levels of cytochrome c contained in a 1536-well microtiter plate are shown. The respective micro- and minisprayer devices provide a simple yet effective means of transferring trace-level samples either from a microscale or chip-based separation device as well as samples contained in multiwell plates which are increasingly employed in high-throughput applications in the pharmaceutical industry.
The New Xpert MTB/RIF Ultra: Improving Detection of <i>Mycobacterium tuberculosis</i> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing (2017)

The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R <i>rpoB</i> mutation detection were tested on <i>Mycobacterium tuberculosis</i> DNA or sputum samples spiked with known numbers of <i>M. tuberculosis</i> H37Rv or <i>Mycobacterium bovis</i> BCG CFU. Frozen and prospectively collected clinical samples from patients suspected of having TB, with and without culture-confirmed TB, were also tested. For <i>M. tuberculosis</i> H37Rv, the LOD was 15.6 CFU/ml of sputum for Ultra versus 112.6 CFU/ml of sputum for Xpert, and for <i>M. bovis</i> BCG, it was 143.4 CFU/ml of sputum for Ultra versus 344 CFU/ml of sputum for Xpert. Ultra resulted in no false-positive RIF-R specimens, while Xpert resulted in two false-positive RIF-R specimens. All RIF-R-associated <i>M. tuberculosis rpoB</i> mutations tested were identified by Ultra. Testing on clinical sputum samples, Ultra versus Xpert, resulted in an overall sensitivity of 87.5% (95% confidence interval [CI], 82.1, 91.7) versus 81.0% (95% CI, 74.9, 86.2) and a sensitivity on sputum smear-negative samples of 78.9% (95% CI, 70.0, 86.1) versus 66.1% (95% CI, 56.4, 74.9). Both tests had a specificity of 98.7% (95% CI, 93.0, 100), and both had comparable accuracies for detection of RIF-R in these samples. Ultra should significantly improve TB detection, especially in patients with paucibacillary disease, and may provide more-reliable RIF-R detection.<b>IMPORTANCE</b> The Xpert MTB/RIF assay (Xpert), the first point-of-care assay for tuberculosis (TB), was endorsed by the World Health Organization in December 2010. Since then, 23 million Xpert tests have been procured in 130 countries. Although Xpert showed high overall sensitivity and specificity with pulmonary samples, its sensitivity has been lower with smear-negative pulmonary samples and extrapulmonary samples. In addition, the prediction of rifampin resistance (RIF-R) in paucibacillary samples and for a few <i>rpoB</i> mutations has resulted in both false-positive and false-negative results. The present study is the first demonstration of the design features and operational characteristics of an improved Xpert Ultra assay. This study also shows that the Ultra format overcomes many of the known shortcomings of Xpert. The new assay should significantly improve TB detection, especially in patients with paucibacillary disease, and provide more-reliable detection of RIF-R.
Subarachnoid hemorrhage in rats (1999)

These data support the hypothesis that hemodilution with molecular hemoglobin decreases hypoperfusion after subarachnoid hemorrhage and that sustained hemodilution is more effective than singular treatment. The data do not support the notion that intravascular DCLHb has an adverse effect on cerebral ischemia after subarachnoid hemorrhage.
Structure and serology of the native polysaccharide antigen of type Ia group B <i>Streptococcus</i> (1980)

The native polysaccharide antigen isolated from type Ia group B Streptococcus by using pH-controlled growth conditions and extraction procedures contains D-galactose, D-glucose, 2-acetamido-2-deoxy-D-glucose, and sialic acid in the molar ratio of 2:1:1:1. The structure of the native type Ia antigen has been elucidated; it can be represented by the following repeating unit in which all the side-chain beta-D-galactopyranose units are masked by sialic acid residues: [Formula: see text] Removal of all the sialic acid groups yields the incomplete type Ia polysacharide antigen with exposed terminal beta-D-galactopyranose residues. Antisera to type Ia organisms produced in rabbits according to the Lancefield procedures contain antibodies specific for both the native and incomplete antigens. Although sialic acid is not itself a determinant in the formation of antibodies to the native polysaccharide, it is an essential part of a larger determinant. In order to maintain the high degree of immunologic specificity of the native antigen, this determinant must be at least a trisaccharide unit, because the native polysaccharide as isolated has terminal disaccharide units [alpha-D-NeuAcp-(2-->3)-beta-D-Galp] identical to those found in the human M and N blood group substances and fetuin. Formation of antibodies to the incomplete antigen is due to determinants terminating in beta-D-galactopyranose residues. These determinants are probably generated by the removal of the masking sialic acid residues from the cell-associated native polysaccharide by degradative processes that occur in organisms grown without pH control.
Chemicals from heavy oils by <scp>ZSM</scp>‐5 catalysis in supercritical water: Model compound and reaction engineering (2020)

Abstract Dodecane cracking and aromatization over ZSM‐5 was studied in the presence and absence of supercritical water (SCW). A group‐type model was used to determine five best‐fit rate constants to describe yields to aliphatics, aromatics, coke, and gases. SCW accelerated gas formation while suppressing coke formation. CO and CO 2 were formed in the presence of SCW, but not in its absence; a new, low‐temperature coke gasification pathway was suggested to account for this observation. Similarly, a low‐temperature alkane reforming pathway was hypothesized to explain the increased relative rate constant for production of gases in the presence of SCW compared with its absence. Additional tests and analysis indicated that these effects could not be ascribed solely to zeolite degradation in the presence of SCW, implying that water directly influences the reaction mechanism. These results provide new insights into the role(s) of water during oil cracking under supercritical conditions.
Real-time content-aware texturing for deformable surfaces (2013)

Animation of models often introduces distortions to their parameterisation, as these are typically optimised for a single frame. The net effect is that under deformation, the mapped features, i.e. UV texture maps, bump maps or displacement maps, may appear to stretch or scale in an undesirable way. Ideally, what we would like is for the appearance of such features to remain feasible given any underlying deformation.
Triode‐type field emission displays with carbon nanotube emitters (2001)

Abstract Carbon nanotube emitters, prepared by screen printing, have demonstrated a great potential towards low‐cost, large‐area field emission displays. Carbon nanotube paste, essential to the screen printing technology, was formulated to exhibit low threshold electric fields as well as an emission uniformity over a large area. Two different types of triode structures, normal gate and undergate, have been investigated, leading us to the optimal structure designing. These carbon nanotube FEDs demonstrated color separation and high brightness over 300 cd/m2 at a video‐speed operation of moving images. Our recent developments are discussed in details.
Periodic separating reactors: Experiments and theory (1989)

Abstract The novel combination of a pressure swing adsorber (PSA) with a periodic flow‐forced packed‐bed reactor is explored. The device provides integral component separation and reaction. Feed sequences studied for the periodic separating reactor (PSR) were those of rapid, single‐bed pressure swing adsorption (RPSA). The experimental investigation employed CO oxidation over a packed bed of supported platinum catalyst and molecular sieve adsorbent. A reaction rate limited model is formulated and solved for a variety of irreversible and reversible reactions. The presence of irreversible chemical reaction is shown to greatly enhance the separation achievable by RPSA alone. For a wide range of inlet CO/O 2 ratios, CO 2 production could be increased up to two times over steady‐state plug‐flow reactor operation, while providing a recycle stream without phase change or extractive procedures. Selectivity and conversion improvements were predicted for multiple reaction systems. Other unusual features of operation, such as separation reversals, were also predicted and observed.
What's the PointiSA? (2014)

Software watermarking, fingerprinting, digital content identification, and many other desirable security properties can be improved with software protection techniques such as tamper resistance and obfuscation. Previous research has demonstrated software protection can be significantly enhanced using a Process-level Virtual Machine (PVM). They can provide robust program protections, particularly at run time, which many other software protection techniques lack. PVMs have been used to provide tamper detection, dynamic code obfuscation, and resistance to static disassembly. Over-all, the presence of PVMs makes it more difficult for the adversary to achieve their goals. Recently, a new attack methodology, called Replacement Attacks, was described that successfully targeted PVM-protected applications. This methodology circumvents execution of the protective PVM instance through the use of another virtual machine to execute the program. The replacement occurs dynamically and allows execution of the application without any PVM-based protections. In this work, we formalize the notion of a replacement attack using a novel model. We then present a defense against such attacks. To the best of our knowledge, this technique is the first defense against replacement attacks. The technique relies on software interpretation of instructions, which forms the basis of PVMs. By carefully modifying the semantics of some individual instructions, it is possible to make the application unusable without the presence of the protective PVM instance. The technique is called PointISA, named after a point function|a function which returns true for only one given input. We provide a formal description of PointISAs and an evaluation of the strength of the approach.
ORF7 of Varicella-Zoster Virus Is a Neurotropic Factor (2012)

Varicella-zoster virus (VZV) is the causative agent of chickenpox and herpes zoster (shingles). After the primary infection, the virus remains latent in sensory ganglia and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine is highly attenuated in the skin and yet retains its neurovirulence and may reactivate and damage sensory neurons. The factors involved in neuronal invasion and establishment of latency are still elusive. Previously, we constructed a library of whole-gene deletion mutants carrying a bacterial artificial chromosome sequence and a luciferase marker in order to perform a comprehensive VZV genome functional analysis. Here, screening of dispensable gene deletion mutants in differentiated neuronal cells led to the identification of ORF7 as the first known, likely a main, VZV neurotropic factor. ORF7 is a virion component localized to the Golgi compartment in infected cells, whose deletion causes loss of polykaryon formation in epithelial cell culture. Interestingly, ORF7 deletion completely abolishes viral spread in human nervous tissue ex vivo and in an in vivo mouse model. This finding adds to our previous report that ORF7 is also a skin-tropic factor. The results of our investigation will not only lead to a better understanding of VZV neurotropism but could also contribute to the development of a neuroattenuated vaccine candidate against shingles or a vector for delivery of other antigens.
Astigmatic mirror multipass absorption cells for long-path-length spectroscopy (1995)

A multipass absorption cell, based on an astigmatic variant of the off-axis resonator (Herriott) configuration, has been designed to obtain long path lengths in small volumes. Rotation of the mirror axes is used to obtain an effective adjustability in the two mirror radii. This allows one to compensate for errors in mirror radii that are encountered in manufacture, thereby generating the desired reentrant patterns with less-precise mirrors. Acombination of mirror rotation and separation changes can be used to reach a variety of reentrant patterns and path lengths with a fixed set of astigmatic mirrors. The accessible patterns can be determined from trajectories, as a function of rotation and separation, through a general map of reentrant solutions. Desirable patterns for long-path spectroscopy can be chosen on the basis of path length, distance of the closest beam spot from the coupling hole, and tilt insensitivity. We describe the mathematics and analysis methods for the astigmatic cell with mirror rotation and then describe the design and test of prototype cells with this concept. Two cell designs are presented, a cell with 100-m path length in a volume of 3 L and a cell with 36-m path length in a volume of 0.3 L. Tests of low-volume absorption cells that use mirror rotation, designed for fast-flow atmospheric sampling, show the validity and the usefulness of the techniques that we have developed.
USING BAYESIAN DECISION THEORY TO DESIGN A COMPUTERIZED MASTERY TEST* (1990)

ABSTRACT Mastery testing is used in educational and certification contexts to decide, on the basis of test performance, whether or not an individual has attained a specified level of knowledge, or mastery, of a given subject. A theoretical framework for mastery testing, based on Item Response Theory and Bayesian decision theory, is described in this paper. In this framework, the idea of sequential testing is developed, with the goal of providing shorter tests for individuals who have clearly mastered (or clearly not mastered) a given subject, and providing longer tests for those individuals for whom the mastery decision is not as clear‐cut. In a simulated application of the approach to a professional certification examination, it is shown that average test lengths can be reduced by half without sacrificing classification accuracy.
Lipidomics-Based Safety Biomarkers for Lipid-Lowering Treatments (2008)

Recent data suggest that aggressive lipid-lowering treatment results in significant reductions of atherosclerotic complications, ie, strokes, heart attacks, or peripheral vascular diseases. Thus, more patients will be titrated to higher doses of statins in order to reach the aggressive targets of low-density lipoprotein- cholesterol reduction. However, aggressive treatment with high statin doses has increased the risk of statin-induced myopathy. The incidence of myopathy in cohort studies and in randomized trials has been low, supporting the good safety profile of statin drugs. However, muscle effects seem to be more frequent in clinical practice. Of all statin users, approximately 1% to 5% suffers from muscular symptoms caused by medication. This potentially reduces the compliance toward treatment and number of patients reaching their treatment targets due to withdrawal of therapy. Thus, novel biomarkers are needed for prediction or improved diagnoses of statin-induced side effects. This would potentially increase the quality of life of patients and improve treatment results. Using lipidomic analysis, we found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein. Intriguingly, these results suggest that the plasma lipidomic profile may serve as a highly sensitive biomarker of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.
Scattering matrix imaging pulse design for real‐time respiration and cardiac motion monitoring (2019)

The S-matrix can be measured during image excitation to generate real-time cardiac and respiratory motion signals for prospective gating. No artefacts are introduced when frequency division multiplexing is used.
A Novel Class of Cyclin-dependent Kinase Inhibitors Identified by Molecular Docking Act through a Unique Mechanism (2009)

The cyclin-dependent kinase (Cdk) family is emerging as an important therapeutic target in the treatment of cancer. Cdks 1, 2, 4, and 6 are the key members that regulate the cell cycle, as opposed to Cdks that control processes such as transcription (Cdk7 and Cdk9). For this reason, Cdks 1, 2, 4, and 6 have been the subject of extensive cell cycle-related research, and consequently many inhibitors have been developed to target these proteins. However, the compounds that comprise the current list of Cdk inhibitors are largely ATP-competitive. Here we report the identification of a novel structural site on Cdk2, which is well conserved between the cell cycle Cdks. Small molecules identified by a high throughput in silico screen of this pocket exhibit cytostatic effects and act by reducing the apparent protein levels of cell cycle Cdks. Drug-induced cell cycle arrest is associated with decreased Rb phosphorylation and decreased expression of E2F-dependent genes. Multiple lines of evidence indicate that the primary mechanism of action of these compounds is the direct induction of Cdk1, Cdk2, and Cdk4 protein aggregation.
Supplementary Figure S1 from Highly Potent, Anthracycline-based Antibody–Drug Conjugates Generated by Enzymatic, Site-specific Conjugation (2023)

<p>Effect of IgG pre-treatment on the in vivo half-life of ADCs in immunodeficient mice.</p>
New non-invasive method and system for intracranial pressure waves' measurement (2002)

Invasive intracranial pressure (ICP) sensors are potentially dangerous for neurosurgical patients. The problem of non-invasive ICP monitoring is analyzed, the new non-invasive method and technique in accordance with the developed ultrasonic transit time method is proposed and a computer based ICP waves' measuring system is introduced. The resolution of this system is less then 0.1 mmHg and the measuring channel's capacity is above 1.0 kbit/s which allows one to resolve up to 11 harmonics of ICP pulse waves. The results of clinical tests and simultaneous comparative analysis of invasive and non-invasive ICP measuring systems' data are shown and discussed.