gebhart/patrepeval huggingface dataset:
Increased Antibody Affinity Confers Broad <i>In Vitro</i> Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus (2012)

Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (K(D)) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection.
Cellular immune selection with hepatitis C virus persistence in humans (2005)

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific cellular immune responses. To determine if immunologically driven sequence variation occurs with HCV persistence, we coordinately analyzed sequence evolution and CD8+ T cell responses to epitopes covering the entire HCV polyprotein in subjects who were followed prospectively from before infection to beyond the first year. There were no substitutions in T cell epitopes for a year after infection in a subject who cleared viremia. In contrast, in subjects with persistent viremia and detectable T cell responses, we observed substitutions in 69% of T cell epitopes, and every subject had a substitution in at least one epitope. In addition, amino acid substitutions occurred 13-fold more often within than outside T cell epitopes (P < 0.001, range 5-38). T lymphocyte recognition of 8 of 10 mutant peptides was markedly reduced compared with the initial sequence, indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These findings reveal two distinct mechanisms of sequence evolution involved in HCV persistence: viral escape from CD8+ T cell responses and optimization of replicative capacity.
Periodic Compounds: Syntheses at High Pressures and Temperatures (1965)

A new class of compounds, called "periodic compounds," identified by the selection rule G = Sigmad(i)e(i)/Sigmad(i), where G assumes the integral values 1, 2, 3, . . . corresponding to the periodic table groups I, II, III, . . ., is discussed. The number of bonding electrons contributed by an atom of kind i is designated e(i), and d(i) gives the number, per formula weight, of atoms of this kind. Both e(i) and d(i) assume integral values. Periodic compounds consist of symmetrical and unsymmetrical types. The recent synthesis of the unsymmetrical periodic compound B(2)O, an isoelectronic analog of carbon, suggests that many more unsymmetrical types may be amenable to synthesis, particularly by high-pressure and high-temperature techniques.
A rapid three-dimensional vortex micromixer utilizing self-rotation effects under low Reynolds number conditions (2005)

This paper proposes a novel three-dimensional (3D) vortex micromixer for micro-total-analysis-systems (μTAS) applications which utilizes self-rotation effects to mix fluids in a circular chamber at low Reynolds numbers (Re). The microfluidic mixer is fabricated in a three-layer glass structure for delivering fluid samples in parallel. The fluids are driven into the circular mixing chamber by means of hydrodynamic pumps from two fluid inlet ports. The two inlet channels divide into eight individual channels tangent to a 3D circular chamber for the purpose of mixing. Numerical simulation of the microfluidic dynamics is employed to predict the self-rotation phenomenon and to estimate the mixing performance under various Reynolds number conditions. Experimental flow visualization by mixing dye samples is performed in order to verify the numerical simulation results. A good agreement is found to exist between the two sets of results. The numerical results indicate that the mixing performance can be as high as 90% within a mixing chamber of 1 mm diameter when the Reynolds number is Re = 4. Additionally, the results confirm that self-rotation in the circular mixer enhances the mixing performance significantly, even at low Reynolds numbers. The novel micromixing method presented in this study provides a simple solution to mixing problems in the lab-chip system.
Pharmacologic Properties of Phenyl <i>N-tert</i> -Butylnitrone (1999)

Phenyl N-tert-butylnitrone (PBN) is the parent of a family of nitrones used as spin-trapping agents to trap free radicals. PBN's pharmacological effects in animal models are extensive, ranging from protection against death after endotoxin shock, protection from ischemia-reperfusion injury, to increasing the life span of mice. Recent additions to the list include protection from bacterial meningitis, thalidomide-induced teratogenicity, drug-induced diabetogenesis, and choline-deficient hepatocarcinogenesis. Because PBN reacts with oxygen radicals to produce less reactive species, it has been suggested that this is the basis of its pharmacological effects. However, there has been no hard evidence for this notation. Nevertheless, many investigators have used the presence of PBN's pharmacologic effect as evidence for free radical involvement in their models. Mechanistic studies on the PBN's antisepsis action revealed that PBN inhibits expression of various pro-inflammatory genes, suggesting that the protective action involves more than a straightforward free radical-scavenging mechanism. Previous and recent developments in the investigations on the pharmacologic properties of PBN are described in this review.
Quadrature Sampling of High-Frequency Waveforms (1968)

The quadrature sampling technique, which obtains samples of the quadrature components of a high-frequency band-limited waveform by direct sampling of the waveform, is shown to lead to an exact interpolation formula. In this formula, the quadrature components of the signal are represented explicitly by low-pass interpolation formulas that greatly facilitate digital processing of the signal when compared to commonly used sampling formulas. For example, the amplitude modulation (envelope) and phase modulation of a signal can be computed directly from these quadrature components.
SSIM-inspired image restoration using sparse representation (2012)

Recently, sparse representation based methods have proven to be successful towards solving image restoration problems. The objective of these methods is to use sparsity prior of the underlying signal in terms of some dictionary and achieve optimal performance in terms of mean-squared error, a metric that has been widely criticized in the literature due to its poor performance as a visual quality predictor. In this work, we make one of the first attempts to employ structural similarity (SSIM) index, a more accurate perceptual image measure, by incorporating it into the framework of sparse signal representation and approximation. Specifically, the proposed optimization problem solves for coefficients with minimum norm and maximum SSIM index value. Furthermore, a gradient descent algorithm is developed to achieve SSIM-optimal compromise in combining the input and sparse dictionary reconstructed images. We demonstrate the performance of the proposed method by using image denoising and super-resolution methods as examples. Our experimental results show that the proposed SSIM-based sparse representation algorithm achieves better SSIM performance and better visual quality than the corresponding least square-based method.
Replication‐deficient adenovirus‐mediated transfer of B7‐1 (CD80) cDNA induces anti‐tumour immunity in isolated human lung cancer (2001)

Objective: Interaction between the co‐stimulatory molecule B7‐1 (CD80) on antigen‐presenting cells and its counter‐receptor CD28 on T lymphocytes plays a key role in the induction of cell‐mediated immune responses. Many tumours, including lung cancer, lack expression of B7‐1 and this has been suggested to contribute to the failure of immune recognition of these diseases. Based on this knowledge, we hypothesized that the co‐stimulatory signal delivered through the B7‐1 molecule expressed on lung cancer cells using replication deficient adenovirus vector would induce efficient tumour immunity in T lymphocytes. Methodology: To evaluate this hypothesis, we constructed two adenovirus vectors: AdCMVhB7 (an E1‐deleted‐Ad5‐based vector containing human B7‐1 cDNA driven by cytomegalovirus immediate early promoter and enhancer) and AdNull (same vector as above without expression of exogenous gene) as control. Using these adenovirus vectors, efficient generation of tumour immunity in T lymphocytes was studied using primary cultured lung cancer cells and peripheral blood lymphocytes (PBL) obtained from patients with lung cancer. Results: Inoculation of lung cancer cells with 10 multiplicity of infection of AdCMVhB7 resulted in rapid and efficient cell surface expression of B7‐1 molecule (> 90% of cells at 24 h). Cytolytic activity of PBL in 51 Cr‐release assay (E/T = 40) demonstrated that effector lymphocytes induced by hB7‐1 (+) lung cancer cells treated with AdCMVhB7could lyse parental lung cancer cells hB7‐1 (–). In contrast, effector lymphocytes induced by lung cancer cells treated with AdNull as control virus or PBS as control could not lyse parental lung cancer cells at all. Furthermore, cytolytic activity of the effector lymphocytes induced by B7‐1‐transduced lung cancer cells was inhibited by addition of anti‐CD3 antibody. Conclusions: These data demonstrate that primary‐cultured lung cancer cells treated with AdCMVhB7 would efficiently generate tumour immunity in T lymphocytes. Adenovirus‐mediated‐hB7‐1 gene transfer may be a useful means for gene therapy of lung cancer using adoptive immunotherapy.
Chinese prosodic phrasing with a constraint-based approach (2005)

The linguistic constraints and phrase-length constraints are the most important factors for Chinese prosodic phrasing in the natural speech. This paper presents a linguistic constraint model and a phrase-length constraint model to describe these two processes independently. Therefore, each part can be described in detail. In the linguistic constraints model, Chunk (base phrase) is considered as an important basic unit. And an HMM is used to model the phrase-length constraints, which concerns the distribution of the prosodic phrase lengths and the relationship between the prosodic phrase and the prosodic words. Then a k-candidate method is introduced to combine these two models. This approach makes full use of the linguistic constraints and the phrase-length constraints. The experiments show that this approach achieved a perfect performance with the phrasing f-score 82.9%.
A Thin-Film Glucose Electrode System with Compensation for Drift (1989)

Thin-film platinum electrodes have been prepared for use in a system for measurement of glucose. Cyclic voltammetry was used to test the electrodes in phosphate and bicarbonate solutions, and in the dialysate of human serum. The peak current output for glucose concentrations between 50-300 mg/dl in a phosphate buffer, and 100-250 mg/dl in the dialysate of human serum, were linear. Two of the three inflection points occurring in the voltammograms are invariant with changes in scan rate, pH, CO2, O2, and glucose. A method for using these points to compensate for voltage drift and current shift is discussed.
Synthesis of monodispersed fcc and fct FePt/FePd nanoparticles by microwave irradiation (2005)

A simple microwave heating method has been used for the stoichiometrically controlled synthesis of FePt and FePd nanoparticles using Na2Fe(CO)4 and Pt(acac)2/Pd(acac)2 as the main reactants. By varying the solvents and surfactants, the microwave assisted reactions have shown a significant advantage for the rapid production of monodisperse fcc FePt nanoparticle metal alloys which can be converted to the fct phase at low temperatures (364 °C). Microwave reactions at high pressure (closed system) have led to the direct formation of a mixture of fcc and fct phase FePt nanoparticles. Room temperature structural and magnetic properties of materials have been characterized by X-ray diffraction, HRTEM and magnetic measurements. The onset of ordering has been investigated by in situ high temperature X-ray diffraction studies.
Effect of Vulcanization on Rubber Structure. A Problem in Probabilities (1940)

Abstract In Goodyear's day, the problem of understanding the process of vulcanization could be expressed by the question: “Why does heating rubber with sulfur keep it from getting soft and tacky on a hot summer day, and hard and boardy in cold winter weather?” The deceptive simplicity of this question probably inspired the hope, which has come down almost to the present day, that the secrets of vulcanization and even of the elasticity of rubber could be explained in terms of the properties and reactions of simple organic molecules, such as the reactions of sulfur with simple olefins. The vast increase in the knowledge of giant molecules during the past decade has shattered any basis there may have been for such a hope, but occasional articles show that this desire for simplicity continues to live and to color our thinking on this problem. This paper discusses some of the inherent limitations of the old, simpler pictures of vulcanization and the structure of rubber, and some of the implications of the present view that crude rubber is built up of giant molecules. Probably there are not merely one or two or half a dozen reactions, but rather there are literally millions of possible vulcanization reactions, each of which may influence the physical properties of the rubber. The study of these reactions will require new and far more sensitive methods of physical and chemical analysis than have been available heretofore, as well as new points of view in interpreting the data.
Controlled synthesis of semiconductor nanostructures in the liquid phase (2011)

The microstructure (composition, size and shape etc.) of semiconductor nanocrystals determine the electronic density of states of semiconductor nanomaterials and ultimately determine their optical and electrical properties. Semiconductor nanocrystal advanced structures, such as hybrid nanostructures and nanocrystal superlattices, not only integrate the function of individual nanocrystals, but also brings the materials collective and synchronic properties. How to control the monodispersity, composition and structure of as-prepared semiconductor nanocrystals during their syntheses, as well as their furthermore assembly, has been a hot research area in this decade. This critical review focuses on the development of synthetic and assembly methods (techniques) of semiconductor nanocrystals processed in the liquid phase. Emphasis is on the synthesis methodology, microstructure related properties of semiconductor nanocrystals, and their applications (243 references).
PHARMACOLOGICAL STUDIES OF NEUTRAL SAPONINS (GNS) OF PANAX GINSENG ROOT (1973)

Pharmacological studies of neutral saponins (GNS) of Panax Ginseng root, were performed. GNS showed CNS-depressant action in inhibition of spontaneous and exploratory movements, and in potentiation of CNS-depressant. A specific blocking action of conditioned response by GNS was significantly confirmed in small doses and did not produce loss of righting reflex, motor incoordination or myo-relaxation. Analgesic, anticonvulsant and antipyretic effects were recognized. From the tests described above in addition to those of traction, hypothermia, fighting behavior and ratio of two reflexes, GNS appears to have neuroleptic activity. There was neither hemolytic nor vasodilator action on the hind leg or coronary vascular beds.
Effects of Adductor Muscle Stimulation on Speech in Abductor Spasmodic Dysphonia (2000)

Adductor muscle stimulation improved speech production in patients with ABSD, and the improvement was greatest in the most severely affected patients. Therefore adductor muscle stimulation has potential for benefiting patients with ABSD.
Mapping of a surface-exposed B-cell epitope to the variable sequent 3 of the major outer-membrane protein of Chlamydia trachomatis (1993)

A B-cell epitope, AEFPLDIT, was located to the variable sequent 3 of the major outer-membrane protein (MOMP) using the monoclonal antibody L3-1, raised to the Chlamydia trachomatis serovar L3 MOMP. By Western blot and inclusion immunofluorescence assay the monoclonal antibody recognized all the C complex and C-related complex serovars of C. trachomatis, except serovar C. Dot-blot and ELISA data using native elementary bodies indicated that the epitope was surface exposed. The monoclonal antibody, at concentrations of 10 and 100 micrograms per 10(7) chlamydial inclusion-forming units, was able to neutralize the infectivity of chlamydia in an in vivo assay but did not neutralize chlamydia in vitro or in a mouse toxicity assay. A peptide corresponding to the variable sequent 3 has previously been shown to also elicit a T-cell response; thus, careful consideration should be given to inclusion of this region of the major outer-membrane protein in a subunit vaccine.
Dynamic Three-Dimensional Shoulder Mri during Active Motion for Investigation of Rotator Cuff Diseases (2016)

The Dynamic MRI enabled a novel measure; 'Looseness', i.e. the translation of the humeral head on the glenoid during an abduction cycle. Looseness was better able at differentiating different forms of rotator cuff disease than a simple static measure of relative glenohumeral position.
Studies of the Active Conformation of a Novel Series of Benzamide Dopamine D2 Agonists (1994)

Analogs of dopamine D2 agonist 11 were prepared in which a rigid trans decalin ring system was used to mimic various conformations of 11. The four rigid analogs where compared for their ability to bind to the DA D2 receptor and to inhibit forskolin-stimulated cAMP formation, a measure of DA agonist activity. Of the four rigid analogs of compound 11, only compound 12b had significant activity in both assays. Molecular modeling studies of 12a-d showed each had a single conformation with regard to the distance between the benzamide aryl-centroid and the 4-nitrogen atom of the pyridylpiperazine. Compound 12b was shown to have a greater distance between these functionalities (11.8 A) as compared to the other isomers (9.8-10.4 A). The distance between these two functionalities in 12b was similar to that of a conformer of 11 which has an extended conformation. This suggest that 11 is likely in an extended conformation when bound to the DA D2 receptor.
Genetic Ablation of Bcl-x Attenuates Invasiveness without Affecting Apoptosis or Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Cancer (2009)

Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-x(L), demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic beta-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-x(L) upon exogenous over-expression.
ChemInform Abstract: STUDIES ON ANTITUBERCULAR AND ANTIBACTERIAL AGENTS: PREPARATION OF 1‐(4‐AMINOBENZOYL)‐2‐BENZALHYDRAZINE AND 1‐(4‐(PHENYLTHIOUREIDO)BENZOYL)‐2‐SUBSTITUTED‐BENZALHYDRAZINE (1985)

Abstract Das Hydrazid (I) reagiert mit den Aldehyden (II) zu den Hydrazonen (IIIa), die mit Phenylisothiocyanat zu den Thioharnstoffen (IIIb) umgesetzt werden.
Colorectal Cancer Screening Comes of Age (1993)

Remarkable progress has been made over the past 25 years in understanding the biologic aspects of colorectal cancer and developing methods to detect it early or even prevent it entirely1. Colorectal cancer arises from a precursor lesion, the adenomatous polyp, which forms in a fertile field of epithelial-cell hyperproliferation. This progression involves a multistep process, accompanied by alterations in several suppressor genes, that results in abnormalities of growth regulation and has a natural history of 10 to 15 years. Environmental factors and inherited susceptibility have major roles in this sequence of events1,2. The long natural history provides . . .
Modeling qRT-PCR dynamics with application to cancer biomarker quantification (2017)

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is widely used for molecular diagnostics and evaluating prognosis in cancer. The utility of mRNA expression biomarkers relies heavily on the accuracy and precision of quantification, which is still challenging for low abundance transcripts. The critical step for quantification is accurate estimation of efficiency needed for computing a relative qRT-PCR expression. We propose a new approach to estimating qRT-PCR efficiency based on modeling dynamics of polymerase chain reaction amplification. In contrast, only models for fluorescence intensity as a function of polymerase chain reaction cycle have been used so far for quantification. The dynamics of qRT-PCR efficiency is modeled using an ordinary differential equation model, and the fitted ordinary differential equation model is used to obtain effective polymerase chain reaction efficiency estimates needed for efficiency-adjusted quantification. The proposed new qRT-PCR efficiency estimates were used to quantify GUCY2C (Guanylate Cyclase 2C) mRNA expression in the blood of colorectal cancer patients. Time to recurrence and GUCY2C expression ratios were analyzed in a joint model for survival and longitudinal outcomes. The joint model with GUCY2C quantified using the proposed polymerase chain reaction efficiency estimates provided clinically meaningful results for association between time to recurrence and longitudinal trends in GUCY2C expression.