gebhart/patrepeval huggingface dataset:
Enzyme Replacement Therapy for Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency (1976)

To evaluate their role as a form of replacement therapy, frozen irradiated red blood cells were administered to a child with adenosine deaminase deficiency associated with severe combined immunodeficiency disease. In vitro lymphocyte responses to mitogens and allogeneic cells were restored. Subsequently, a "thymus shadow" appeared, and immunoglobulin synthesis was demonstrated. Frozen irradiated plasma, which alone had no effect on lymphocytes numbers or responses, promoted lymphocytosis when given with frozen irradiated red blood cells. The patient received the transfusions with or without irradiated plasma at four-week intervals and remained free of infection for 17 months. The patient's lymphocyte adenosine triphosphate levels were elevated before therapy, which consistently reduced them without altering the lymphocyte adenosine deaminase activity. Enzyme replacement therapy may provide a way to treat patients with adenosine deaminase deficiency associated with severe combined immunodeficiency disease who do not have histocompatible bone-marrow donors.
Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads (2011)

We demonstrate a three-step assay on a silicon photonic microring resonator-based detection platform that enables the quantitation of the cardiac biomarker C-reactive protein (CRP) over a dynamic range spanning six orders of magnitude. Using antibody-modified microrings, we sequentially monitor primary CRP binding, secondary recognition of bound CRP by a biotinylated antibody, and tertiary signal amplification using streptavidin-functionalized beads. This detection methodology is applied to CRP quantitation in human serum and plasma samples.
The use of very long chain polyunsaturated fatty acids to ameliorate metabolic syndrome: transgenic plants as an alternative sustainable source to fish oils (2004)

Summary Awareness of the increased prevalence of heart disease, obesity and type 2 diabetes has resulted in research being focused on simple and robust approaches to their prevention. One rationale for dealing with these potentially major public health problems is via a better understanding of the contribution of diet to progression towards these diseased states. As a response to these concerns, major research efforts in this area have been funded under the auspices of the European Union. In particular, studies are aimed at providing the scientific basis for improving health through diet, with a focus on understanding how polyunsaturated fish oils can be a positive ( i.e. protective) component of diet against metabolic syndrome (the descriptor for progression towards diseases such as obesity and type 2 diabetes). This review will consider the health implications of the rise in metabolic syndrome, as well as new approaches to the provision of beneficial polyunsaturated oils.
Attenuation of Phospholipid Signaling Provides a Novel Mechanism for the Action of Valproic Acid (2007)

Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PH(Crac)-green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP(3)) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP(2) phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis-processes previously shown to be dependent upon PIP(3) production. These results suggest that in Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug.
Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis (2011)

Increased serum levels of CO5-1230 were associated with the extent of collagen deposition in two different models of fibrotic processes in the liver. The data indicate that formation of type V collagen may be of value as a disease-specific diagnostic biomarker that reflects the total burden of disease. The amino acid sequence selected is located in the first 10 amino acids of the C-terminal propeptide section, which is a formation-specific region.
Narrow and wide band estimates of field strength for indoor communications in the millimetre band (1991)

A simple multifloor multireflection and transmission model is used to explore the possible use of the 60 GHz frequency range for indoor cordless communications. Whether using vertical or horizontal transmitted polarisation the dynamic range between maxima and notches of field strength against frequency is not as great as first feared. Thus it would appear that communications within a picocell may well have to cope with signals with varying strength ranging only between 30-40 dB, at worst, and most likely within half of that range.
Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate. (1992)

Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+ cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.
The chromosomal analysis of human oocytes. An overview of established procedures (2004)

The cytogenetic survey of mature human oocytes has been and remains a subject of great interest because of the prevalence of aneuploidy of maternal origin in abnormal human conceptuses, and the lack of understanding about the non-disjunction processes in human meiosis. The first attempts to analyse the chromosomal content of human female gametes were made in the early 1970s, and led to limited data because of the paucity of materials and the inadequacy of the procedure used. The years to follow brought a resurgence of interest in this field, because of the development of human IVF techniques which made oocytes unfertilized in vitro available for cytogenetic analysis. Numerous studies have since been performed. However, the difficulties in obtaining good chromosome preparations and of performing accurate chromosome identification have reduced the viability of these studies, resulting in large variations in the reported incidences of chromosomal abnormalities. The further introduction of new procedures for oocyte fixation and the screening of large oocyte samples have allowed more reliable data to be obtained and to identify premature chromatid separation as a major mechanism in aneuploidy occurrence. The last decade has been privileged to witness the adaptation of molecular cytogenetic techniques to human oocytes, and thus various powerful procedures have been tried not only on female gametes, but also on polar bodies, involving sequential and multicolour fluorescent in situ hybridization (FISH) labelling, comparative genomic hybridization (CGH), spectral karyotyping and alternative methods such as primed in situ labelling (PRINS) and peptide nucleic acid (PNA) techniques. A large body of data has been obtained, but these studies also display a great variability in the frequency of abnormalities, which may be essentially attributable to the technical limitations of these in situ methods when applied to human oocytes. However, molecular cytogenetic approaches have also evidenced the co-existence of both whole chromosome non-disjunction and chromatid separation in maternal aneuploidy. In addition, the extension of these techniques to oocyte polar body materials has provided additional data on the mechanism of meiotic malsegregation. Improvements of some of these techniques have already been reported. The further development of new approaches for the in situ analysis of human meiosis will increase the impact of cytogenetic investigation of human oocytes in the understanding of aneuploidy processes in humans.
Thermopower enhancement in lead telluride nanostructures (2004)

We demonstrate an enhancement in the thermopower of PbTe nanostructures with grain sizes on the order of $30--50\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$, relative to bulk. The enhancement is similar in magnitude to that reported in the literature for $\mathrm{Pb}\mathrm{Te}∕\mathrm{Pb}{\mathrm{Se}}_{x}{\mathrm{Te}}_{1\ensuremath{-}x}$ quantum dot superlattices. We provide proof, based on measurements of the transverse Nernst effect, that the enhancement has its origin in electron energy filtering induced by an alteration of the scattering mechanism.
Minimal 2'-O-methyl phosphorothioate linkage modification pattern of synthetic guide RNAs for increased stability and efficient CRISPR-Cas9 gene editing avoiding cellular toxicity (2017)

Since its initial application in mammalian cells, CRISPR-Cas9 has rapidly become a preferred method for genome engineering experiments. The Cas9 nuclease is targeted to genomic DNA using guide RNAs (gRNA), either as the native dual RNA system consisting of a DNA-targeting CRISPR RNA (crRNA) and a trans-activating crRNA (tracrRNA), or as a chimeric single guide RNA (sgRNA). Entirely DNA-free CRISPR-Cas9 systems using either Cas9 protein or Cas9 mRNA and chemically synthesized gRNAs allow for transient expression of CRISPR-Cas9 components, thereby reducing the potential for off-targeting, which is a significant advantage in therapeutic applications. In addition, the use of synthetic gRNA allows for the incorporation of chemical modifications for enhanced properties including improved stability. Previous studies have demonstrated the utility of chemically modified gRNAs, but have focused on one pattern with multiple modifications in co-electroporation with Cas9 mRNA or multiple modifications and patterns with Cas9 plasmid lipid co-transfections. Here we present gene editing results using a series of chemically modified synthetic sgRNA molecules and chemically modified crRNA:tracrRNA molecules in both electroporation and lipid transfection assessing indel formation and/or phenotypic gene knockout. We show that while modifications are required for co-electroporation with Cas9 mRNA, some modification patterns of the gRNA are toxic to cells compared to the unmodified gRNA and most modification patterns do not significantly improve gene editing efficiency. We also present modification patterns of the gRNA that can modestly improve Cas9 gene editing efficiency when co-transfected with Cas9 mRNA or Cas9 protein (> 1.5-fold difference). These results indicate that for certain applications, including those relevant to primary cells, the incorporation of some, but not all chemical modification patterns on synthetic crRNA:tracrRNA or sgRNA can be beneficial to CRISPR-Cas9 gene editing.
Intradermal Delivery of Adenoviral Type-35 Vectors Leads to High Efficiency Transduction of Mature, CD8+ T Cell-Stimulating Skin-Emigrated Dendritic Cells (2006)

Recombinant adenovirus (Ad) type 35 (rAd35) shows great promise as vaccine carrier with the advantage of low pre-existing immunity in human populations, in contrast to the more commonly used rAd5 vector. The rAd35 vector uses CD46 as a high-affinity receptor, which, unlike the rAd5 receptor, is expressed on human dendritic cells (DC), the most powerful APCs identified to date. In this study, we show that in contrast to rAd5, rAd35 infects migrated and mature CD83+ cutaneous DC with high efficiency (up to 80%), when delivered intradermally in an established human skin explant model. The high transduction efficiency is in line with high expression levels of CD46 detected on migratory cutaneous DC, which proved to be further increased upon intradermal administration of GM-CSF and IL-4. As compared with Ad5, these Ad35 infection characteristics translate into higher absolute numbers of skin-emigrated DC per explant that both express the transgene and are phenotypically mature. Finally, we demonstrate that upon intracutaneous delivery of a rAd35 vaccine encoding the circumsporozoite (CS) protein of Plasmodium falciparum, emigrated DC functionally express and process CS-derived epitopes and are capable of activating specific CD8+ effector T cells, as evidenced by activation of an HLA-A2-restricted CS-specific CD8+ T cell clone. Collectively, these data demonstrate the utility of rAd35 vectors for efficient in vivo human DC transduction.
A Biomechanical Study of the Fatigue Characteristics of Thoracolumbar Fixation Implants in a Calf Spine Model (1992)

Clinical failures of internal fixation implants for the treatment of the thoracolumbar spine are generally attributed to fatigue. Few studies, however, have characterized changes in fixation rigidity with time or subjected spine-implant fixation constructs to fatigue loading until failure. Fatigue characteristics of five dorsally applied spinal fixation implants were determined using lumbosacral calf spines, with an L3 vertebrectomy, loaded cyclically in combined compression (maximum 605 N) and flexion (maximum 16 Nm) for up to 100,000 cycles. Displacement transducers monitored motion at the site of instability and at the segment above the implants. Flexibility and strain at these segments were then calculated. A one-way analysis of variance showed that there were no significant differences in flexibility of the five fixation constructs (P greater than .05). A multiple Bonferroni test revealed that the AO and Kluger fixateur interne and Steffee plates, with fixation at L2 and L4, allowed significantly more strain (P less than .01) across the site of instability than did Harrington rods and Luque plates with fixation at L1, L2, L4, and L5. There were no significant differences between fixation constructs in initial strain above the implants. After 10,000 cycles, however, there were significant increases in strain across the segment above the Luque and Harrington implants (P less than .05). Failure of the AO Schanz screw occurred in three of six constructs at a mean of 73,300 cycles. The Steffee screws failed in four of five constructs at a mean of 20,800 cycles. The rods of the Kluger fixateur interne broke in four of five constructs at a mean of 47,800 cycles, and one screw slipped at 11,000 cycles. There were no metal failures in the Harrington or Luque implants.(ABSTRACT TRUNCATED AT 250 WORDS)
Oral Treatment with Lactococcus lactis Expressing Staphylococcus hyicus Lipase Enhances Lipid Digestion in Pigs with Induced Pancreatic Insufficiency (2002)

The Staphylococcus hyicus lip gene was cloned in Lactococcus lactis. Pancreatic insufficiency was induced by ligation of the pancreatic duct in pigs. In pigs who had undergone pancreatic ligation, the coefficient of fat absorption was higher after consumption of lipase-expressing L. lactis (91.9% +/- 3.7%) than that after consumption of the inactive control strain (78.4% +/- 2.4%).
Theoretical foundations of transform coding (2001)

Discusses various aspects of transform coding, including: source coding, constrained source coding, the standard theoretical model for transform coding, entropy codes, Huffman codes, quantizers, uniform quantization, bit allocation, optimal transforms, transforms visualization, partition cell shapes, autoregressive sources, transform optimization, synthesis transform optimization, orthogonality and independence, and departures form the standard model.
Introduction: Localités and Nationalism as the Vestigial and the lncipient? (2000)

The professionalization of history was tightly bound to nationalism. Historians in early modern Europe distinguished between story and inventory: chronology and chorography. The latter was the domain of the local antiquarian and county historian.3 Nineteenth-century historians sought to validate their narratives as the story of something important, the growth of the nation-state. The earliest professional journals and organizations-The English Historical Review (first published in 1886), the American Historical Association (founded in 1884 and incorporated by Congress in 1889)-were national. Even as local history professionalized and cut its antiquarian/chorographical roots, the profession still marginalized it, and local history was mainly published by antiquarian or local societies. Thus, for example, even though the Transactions cf the Woolhope Naturalists' Field Club included Herefordshire history when it began publishing in 1852, The English Historical Review claims to be "the oldest journal of historical scholarship in the English-speaking world." Even those who carved out a field distinct from national history, such as the German genre of Landesgeschicte (regional or provincial history), were considered subordinate if not actually suspect endeavors by the profession. Recently, however, European historians have embraced the locality and the region not just as a convenient sample or area of analysis, but as the salient tool to understand continental historical development. In contrast to the modernizing thesis of works from the 1960s and 1970s, such as Eugen Weber's Peasants into Frenchmen: the Modernization of Rural France, /87U- JY l.f (Stanford, I 979), recent books include Celia Applegate, A Nation of Provincials: The German Idea of Heimat (Berkeley, 1990) and Alon Confino, The Nation as a Local Metaphor: Wiirtemberg, Imperial Germany, and National Memory, 1871-1918 (Chapel Hill, 1997). More recently, Celia Applegate delivered a paper on "A Europe of Regions" as part of an American Historical Review Forum "Bringing Regionalism Back to History."
Market Microstructure and Market Liquidity (1999)

This paper explores the factors affecting market liquidity using a simulation model of an artificial market. We first survey definition of market liquidity and discuss the relationship between market liquidity and market efficiency or stability. We then consider a continuous auction market and discuss factors affecting market liquidity. Incorporating the discussion, we construct an artificial market model and conduct various simulations. We find that an increase in the ratio of market participants following short-term market price movements results in an increase in the number of trades and at the same time a decrease in the volume of accumulated order flows. When market participants become more risk-averse on average, market liquidity decreases. A precipitous decrease in market liquidity results when market participants lose confidence in their expectations on future prices. Changes in the sensitivities of traders to market information affect market liquidity, but various market liquidity indicators do not necessarily move in the same direction. These results suggest that change in market liquidity indicators may not always be consistent. * Views expressed in this paper are those of the authors and not necessarily those of the Bank of Japan, the Committee on the Global Financial System, or the Bank for International Settlements.
Construction of a food-grade host/vector system for Lactococcus lactis based on the lactose operon (1995)

A plasmid-based food-grade vector system was developed for Lactococcus lactis by exploiting the genes for lactose metabolism. L. lactis MGS267 is a plasmid-free strain containing the entire lactose operon as a chromosomal insertion. The lacF gene was deleted from this strain by a double cross-over homologous recombination event. The lacF-deficient strain produced a Lac− phenotype on indicator agar. A cloned copy of the lacF gene expressed on a plasmid was capable of complementing the lacF-deficient strain resulting in a Lac+ phenotype. This stably maintained system fits the requirements of a self-selecting vector system and has the potential to be exploited in the food industry.
Microwave Generation Based on Optical Domain Microwave Frequency Octupling (2009)

A novel approach to achieving microwave frequency octupling in the optical domain is proposed and demonstrated. The proposed system consists of two cascaded Mach-Zehnder modulators (MZMs) that are both biased at the maximum transmission point, with a tunable optical phase shifter connected in between to introduce a phase shift. An input microwave signal is applied to the MZMs with its power adjusted to ensure the two MZMs having an identical phase modulation index. A theoretical analysis that leads to the conditions for achieving frequency octupling is provided. The approach is verified by experiments. The phase noise performance and the frequency tunability are also experimentally investigated.
Derivatives of the thebaine anion. 2. 5-Methylmorphine, 5-methylcodeine, 5-methylheroin and some related compounds (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDerivatives of the thebaine anion. 2. 5-Methylmorphine, 5-methylcodeine, 5-methylheroin and some related compoundsMarshall Gates, Richard M. Boden, and P. SundararamanCite this: J. Org. Chem. 1989, 54, 4, 972–974Publication Date (Print):February 1, 1989Publication History Published online1 May 2002Published inissue 1 February 1989https://pubs.acs.org/doi/10.1021/jo00265a046https://doi.org/10.1021/jo00265a046research-articleACS PublicationsRequest reuse permissionsArticle Views236Altmetric-Citations19LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts