gebhart/patrepeval huggingface dataset:
Antibody regulation of T-cell immunity: implications for vaccine strategies against intracellular pathogens (2004)

Intracellular microbial pathogens cause a plethora of diseases that pose a huge public health challenge. Efficacious prophylactic vaccines are needed to protect the population from this myriad of infectious diseases. Contemporary approaches to vaccine design are guided by the immunobiological paradigm that extracellular pathogens are controlled principally by humoral immunity, involving specific antibodies, whereas host protection against intracellular pathogens requires effectors of cell-mediated immunity. However, this distinct T-helper (Th) type 1 and 2 paradigm of host defense has encountered a major challenge due to the reality that most antigens or vaccines induce mixed immune responses comprising of both humoral and CMI effectors. Besides, the true functional independence of antibodies and T-cells under in vivo physiologic conditions is uncertain. Recent findings have revealed that antibodies exert a significant immunoregulatory effect on T-cell immunity. Thus, a robust and protective T-cell memory response against microbial pathogens such as Chlamydia and Mycobacteria require an effective primary humoral immune response characterized by specific antibody isotypes whose role is to modulate Th1 activation via Fc receptors (FcR) by facilitating a rapid uptake, processing and presentation of pathogen-derived antigens for an enhanced T-cell response. These findings have crystallized into a paradigm shift in host defense wherein different components of the apparently disparate mixed immune responses elicited against a microbial pathogen function concertedly to maximize the principal effector mechanism. This review focuses on the essential role of both arms of the immune system in controlling intracellular microbial pathogens, especially the regulatory role of FcR-mediated antibody function in optimizing the induction of a protective Th1 response. The immunobiological implications are discussed in the context of vaccine design, delivery and evaluation against intracellular microbial pathogens of bacteria, fungi and parasitic origin.
Impacts of Sample Preparation Methods on Solubility and Antilisterial Characteristics of Essential Oil Components in Milk (2013)

Essential oil components (EOCs) have limited water solubility and are used at much higher concentrations in complex food matrices than in growth media to inhibit pathogens. However, the correlation between solubility and activity has not been studied. The objective of this work was to characterize the solubility of EOCs in solvents and milk and correlate solubility with antilisterial activity. The solubilities of four EOCs, thymol, carvacrol, eugenol, and trans-cinnamaldehyde, in water was significantly increased in the presence of 5% (vol/vol) ethanol. In milk, the solubility of EOCs was lower than in water, with lower solubility in higher-fat milk. EOCs applied to milk as stock solutions (in 95% aqueous ethanol) enabled quicker dissolution and higher solubility in milk serum than other methods of mixing, such as end to end, and greater reductions of Listeria monocytogenes Scott A after 0 and 24 h. When the EOC concentration detected in milk serum was above the minimum bactericidal concentration, complete inhibition of L. monocytogenes in tryptic soy broth resulted. Therefore, the antilisterial properties in milk could be correlated with the solubility by comparison to the minimum inhibitory or bactericidal concentrations of EOCs. While the EOCs applied using ethanol generally had solubility and activity characteristics superior to those of other mixing methods, ethanol is not used to a great extent in nonfermented foods. Therefore, mixing methods without an organic solvent may be more readily adaptable to enhancing the distribution of EOCs in complex food systems.
5 The Fidelity of Retroviral Reverse Transcriptases (1993)

The reported rate at which mutations are generated in retroviruses ranges from 10 −6 to 10 −4 mutations per nucleotide per cycle through a host cell (Batschelet 1976; Leider et al. 1988; Pathak and Temin 1990). Hyper-mutagenesis in spleen necrosis virus (SNV) (Pathak and Temin 1990) is one special case where the rate is even higher, 10 −2 . Such mutation rates are considerably higher than those of DNA-based microbes (Drake 1991), which range from 10 −7 to 10 −11 mutations per nucleotide per generation. Analogous to the situation in DNA-based organisms, retroviral diversity presumably results from several competing forces (Drake 1991), including the disadvantage of deleterious mutations, the advantage of rapid adaptation to a changing environment in the host, and the cost in terms of the energy required to avoid or eliminate mutations. Three different replication systems operate during the life cycle of a retrovirus. The reverse transcriptase (RT) polymerizes deoxyribonucleotides, first using viral RNA and then the newly made complementary strand DNA as a template. Cellular DNA polymerases replicate the integrated viral DNA. Finally, RNA polymerase II transcribes the proviral DNA into RNA genomes that are packaged into virions. Although it is possible for mutations to be introduced into the viral genome during any one of these replication steps, much attention has focused on the subject of this chapter, i.e., the fidelity of DNA synthesis catalyzed by RTs. We begin this review by describing the steps that determine fidelity during DNA polymerization reactions, and then we consider several models for how DNA polymerases make...
Capillary zone electrophoresis of proteins in untreated fused silica tubing (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCapillary zone electrophoresis of proteins in untreated fused silica tubingHenk H. Lauer and Douglass. McManigillCite this: Anal. Chem. 1986, 58, 1, 166–170Publication Date (Print):January 1, 1986Publication History Published online1 May 2002Published inissue 1 January 1986https://doi.org/10.1021/ac00292a041Request reuse permissionsArticle Views1020Altmetric-Citations516LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (641 KB) Get e-Alertsclose Get e-Alerts
Experimental implementation of dynamic access ordering (1994)

As microprocessor speeds increase, memory bandwidth is rapidly becoming the performance bottleneck in the execution of vector-like algorithms. Although caching provides adequate performance for many problems, caching alone is an insufficient solution for vector applications with poor temporal and spatial locality. Moreover, the nature of memories themselves has changed. Current DRAM components should not be treated as uniform access-time RAM: achieving greater bandwidth requires exploiting the characteristics of components at every level of the memory hierarchy. The authors describe hardware-assisted access ordering and a hardware development effort to build a Stream Memory Controller (SMC) that implements the technique for a commercially available high-performance microprocessor, the Intel i860. The strategy augments caching by combining compile-time detection of memory access patterns with a memory subsystem that decouples the order of requests generated by the processor from that issued to the memory system. This decoupling permits requests to be issued in an order that optimizes use of the memory system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Presence of leptin receptors in rat small intestine and leptin effect on sugar absorption (1998)

Leptin is involved in food intake and thermogenesis regulation. Since leptin receptor expression has been found in several tissues including small intestine, a possible role of leptin in sugar absorption by the intestine was investigated. Leptin inhibited D-galactose uptake by rat small intestinal rings 33% after 5 min of incubation. The inhibition increased to 56% after 30 min. However, neither at 5 min nor at 30 min did leptin prevent intracellular galactose accumulation. This leptin effect was accompanied by a decrease of the active sugar transport apparent Vmax (20 vs. 4.8 micromol/g wet weight 5 min) and apparent Km (15.8 vs. 5.3 mM) without any change in the phlorizin-resistant component. On the other hand, immunohistochemical experiments using anti-leptin monoclonal antibodies recognized leptin receptors in the plasma membrane of immune cells located in the lamina propria. These results indicate for the first time that leptin has a rapid inhibitory effect on sugar absorption and demonstrate the presence of leptin receptors in the intestinal mucosa.
Slide rule (2008)

Recent advances in touch screen technology have increased the prevalence of touch screens and have prompted a wave of new touch screen-based devices. However, touch screens are still largely inaccessible to blind users, who must adopt error-prone compensatory strategies to use them or find accessible alternatives. This inaccessibility is due to interaction techniques that require the user to visually locate objects on the screen. To address this problem, we introduce Slide Rule, a set of audio-based multi-touch interaction techniques that enable blind users to access touch screen applications. We describe the design of Slide Rule, our interaction techniques, and a user study in which 10 blind people used Slide Rule and a button-based Pocket PC screen reader. Results show that Slide Rule was significantly faster than the button-based system, and was preferred by 7 of 10 users. However, users made more errors when using Slide Rule than when using the more familiar button-based system.
Parkin promotes intracellular A 1-42 clearance (2009)

Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases that may share some underlying mechanisms of pathogenesis. Abeta(1-42) fragments are found intracellularly, and extracellularly as amyloid plaques, in Alzheimer's disease and in dementia with Lewy Bodies. Parkin is an E3-ubiquitin ligase involved in proteasomal degradation of intracellular proteins. Mutations in parkin, which result in loss of parkin function, lead to early onset Parkinsonism. Here we tested whether the ubiquitin ligase activity of parkin could lead to reduction in intracellular human Abeta(1-42). Lentiviral constructs encoding either human parkin or human Abeta(1-42) were used to infect M17 neuroblastoma cells. Parkin expression resulted in reduction of intracellular human Abeta(1-42) levels and protected against its toxicity in M17 cells. Co-injection of lentiviral constructs into control rat primary motor cortex demonstrated that parkin co-expression reduced human Abeta(1-42) levels and Abeta(1-42)-induced neuronal degeneration in vivo. Parkin increased proteasomal activity, and proteasomal inhibition blocked the effects of parkin on reducing Abeta(1-42) levels. Incubation of Abeta(1-42) cell lysates with ubiquitin, in the presence of parkin, demonstrated the generation of Abeta-ubiquitin complexes. These data indicate that parkin promotes ubiquitination and proteasomal degradation of intracellular Abeta(1-42) and demonstrate a protective effect in neurodegenerative diseases with Abeta deposits.
MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis (2012)

miR-221/222 may be new markers for stellate cell activation and liver fibrosis progression.
Connexins and Gap Junctions in the Inner Ear (2002)

Mutations in the genes for three different isotypes of the gap junction channel protein connexin are associated with deafness. This indicates an important role for gap junctions in auditory function and provides an opportunity to explore structure-function relationships in the connexin molecule. We have been examining the distribution of gap junctions and the pattern of connexin expression in the mature inner ear and during development, and the effect of specific mutations on the processing and functionality of the expressed connexin proteins in an in vitro system.
Large mesh deformation using the volumetric graph Laplacian (2005)

We present a novel technique for large deformations on 3D meshes using the volumetric graph Laplacian. We first construct a graph representing the volume inside the input mesh. The graph need not form a solid meshing of the input mesh's interior; its edges simply connect nearby points in the volume. This graph's Laplacian encodes volumetric details as the difference between each point in the graph and the average of its neighbors. Preserving these volumetric details during deformation imposes a volumetric constraint that prevents unnatural changes in volume. We also include in the graph points a short distance outside the mesh to avoid local self-intersections. Volumetric detail preservation is represented by a quadric energy function. Minimizing it preserves details in a least-squares sense, distributing error uniformly over the whole deformed mesh. It can also be combined with conventional constraints involving surface positions, details or smoothness, and efficiently minimized by solving a sparse linear system.We apply this technique in a 2D curve-based deformation system allowing novice users to create pleasing deformations with little effort. A novel application of this system is to apply nonrigid and exaggerated deformations of 2D cartoon characters to 3D meshes. We demonstrate our system's potential with several examples.
Multilayer optical learning networks (1987)

A new approach to learning in a multilayer optical neural network based on holographically interconnected nonlinear devices is presented. The proposed network can learn the interconnections that form a distributed representation of a desired pattern transformation operation. The interconnections are formed in an adaptive and self-aligning fashioias volume holographic gratings in photorefractive crystals. Parallel arrays of globally space-integrated inner products diffracted by the interconnecting hologram illuminate arrays of nonlinear Fabry-Perot etalons for fast thresholding of the transformed patterns. A phase conjugated reference wave interferes with a backward propagating error signal to form holographic interference patterns which are time integrated in the volume of a photorefractive crystal to modify slowly and learn the appropriate self-aligning interconnections. This multilayer system performs an approximate implementation of the backpropagation learning procedure in a massively parallel high-speed nonlinear optical network.
Visual Cues in Estimation of Part-To-Whole Comparisons (2019)

Pie charts were first published in 1801 by William Playfair and have caused some controversy since. Despite the suggestions of many experts against their use, several empirical studies have shown that pie charts are at least as good as alternatives. From Brinton to Few on one side and Eells to Kosara on the other, there appears to have been a hundred-year war waged on the humble pie. In this paper a set of experiments are reported that compare the performance of pie charts and horizontal bar charts with various visual cues. Amazon's Mechanical Turk service was employed to perform the tasks of estimating segments in various part-to-whole charts. The results lead to recommendations for data visualization professionals in developing dashboards.
Field Detection of Francisella tularensis (2000)

A field investigation was undertaken following an outbreak of water-borne tularemia in Northern Norway. Francisella tularensis bacterial cellular components were analysed by rapid immunochromatography (RI)-testing, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Water from 1 reservoir, fed from a rapid stream, tested negative. From another reservoir, 2 of a chain of 3 wells tested negative. The third well, at the end of the chain, contained lemming (Lemmus lemmus) carcasses and gave ample proof of F. tularensis contamination. We concluded that the origin of the outbreak was dead, infective lemming carcasses in the water sources. For the various sampling materials, the RI-test proved itself particularly handy and versatile, compared with the ELISA and the PCR.
Selective deoxygenation and modification at C2' of nucleosides. (1982)

Treatment of nucleosides with 1,1,3,3-tetraisopropyl-1,3-dichlorodisiloxane in pyridine gives the 3',5'-O-(1,1,3,3-tetraisopropyldisilox-1,3-diyl) derivatives in high yields. These selectively protected 3',5'-O-TPDS-nucleosides can be functionalized readily at 02'. Deoxygenation of beta-ribonucleosides affords the 2'-deoxy-beta-D-erythro-pentofuranosyl compounds. Analogous treatment of alpha-arabinonucleosides provides a stereoselective route to the 2'-deoxy-alpha-D-erythro-pentofuranosyl products. Sequential oxidation and reduction of 3',5'-O-TPDS-beta-ribonucleosides gives the beta-arabinonucleosides. Triflation followed by nucleophilic displacements converts 3',5'-O-TPDS-ribo and arabinonucleosides to their corresponding 2'-deoxy-2'-substituted arabino and ribo analogues, respectively.
Spatial-heterodyne spectrometer for transmission-Raman observations (2017)

A new transmission Raman spectrometer has been developed using a spatial heterodyne spectrometer (SHS), taking advantage of the high etendue inherent in this class of spectrometer to maximize the light collected from the target. The system has been tested against paracetamol tablet samples. The instrument has been shown to accept light from 0.05 mm up to a 3 mm core diameter fibre bundle with a numerical aperture of 0.22, whilst no degradation in resolution is observed.
Proteomics by Mass Spectrometry: Approaches, Advances, and Applications (2009)

Mass spectrometry (MS) is the most comprehensive and versatile tool in large-scale proteomics. In this review, we dissect the overall framework of the MS experiment into its key components. We discuss the fundamentals of proteomic analyses as well as recent developments in the areas of separation methods, instrumentation, and overall experimental design. We highlight both the inherent strengths and limitations of protein MS and offer a rough guide for selecting an experimental design based on the goals of the analysis. We emphasize the versatility of the Orbitrap, a novel mass analyzer that features high resolution (up to 150,000), high mass accuracy (2-5 ppm), a mass-to-charge range of 6000, and a dynamic range greater than 10(3). High mass accuracy of the Orbitrap expands the arsenal of the data acquisition and analysis approaches compared with a low-resolution instrument. We discuss various chromatographic techniques, including multidimensional separation and ultra-performance liquid chromatography. Multidimensional protein identification technology (MudPIT) involves a continuum sample preparation, orthogonal separations, and MS and software solutions. We discuss several aspects of MudPIT applications to quantitative phosphoproteomics. MudPIT application to large-scale analysis of phosphoproteins includes (a) a fractionation procedure for motif-specific enrichment of phosphopeptides, (b) development of informatics tools for interrogation and validation of shotgun phosphopeptide data, and (c) in-depth data analysis for simultaneous determination of protein expression and phosphorylation levels, analog to western blot measurements. We illustrate MudPIT application to quantitative phosphoproteomics of the beta adrenergic pathway. We discuss several biological discoveries made via mass spectrometry pipelines with a focus on cell signaling proteomics.
Cytogenetics for the model system Arabidopsis thaliana (1998)

A detailed karyotype of Arabidopsis thaliana is presented using meiotic pachytene cells in combination with fluorescence in situ hybridization. The lengths of the five pachytene bivalents varied between 50 and 80 microns, which is 20-25 times longer than mitotic metaphase chromosomes. The analysis confirms that the two longest chromosomes (1 and 5) are metacentric and the two shortest chromosomes (2 and 4) are acrocentric and carry NORs subterminally in their short arms, while chromosome 3 is submetacentric and medium sized. Detailed mapping of the centromere position further revealed that the length variation between the pachytene bivalents comes from the short arms. Individual chromosomes were unambiguously identified by their combinations of relative lengths, arm-ratios, presence of NOR knobs and FISH signals with a 5S rDNA probe and chromosome specific DNA probes. Polymorphisms were found among six ecotypes with respect to the number and map positions of 5S rDNA loci. All ecotypes contain 5S rDNA in the short arms of chromosomes 4 and 5. Three different patterns were observed regarding the presence and position of a 5S rDNA locus on chromosome 3. Repetitive DNA clones enabled us to subdivide the pericentromeric heterochromatin into a central domain, characterized by pAL1 and 106B repeats, which accommodate the functional centromere and two flanking domains, characterized by the 17 A20 repeat sequences. The upper flanking domains of chromosomes 4 and 5, and in some ecotypes also chromosome 3, contain a 5S rDNA locus. The detection of unique cosmids and YAC sequences demonstrates that detailed physical mapping of Arabidopsis chromosomes by cytogenetic techniques is feasible. Together with the presented karyotype this makes Arabidopsis a model system for detailed cytogenetic mapping.
Curing “Incurable” Cancer (2011)

Cancer cells are preferentially killed by anticancer agents because key signals for growth and cell division are "always on" as opposed to the alternative "on" and "off" signaling of normal cells. Too much of today's anticancer drug discovery effort may go toward reversing genetically promoted "always on" signals. More effective anticancer drug targets may be found through use of RNAi technologies that pinpoint the key gene regulatory and metabolic weakness of the "always on" cancer cells.