gebhart/patrepeval huggingface dataset:
Analyzing the Therapeutic Efficacy of Bis-Choline-Tetrathiomolybdate in the Atp7b−/− Copper Overload Mouse Model (2021)

Bis-choline-tetrathiomolybdate, introduced as WTX101 (now known as ALXN1840), is a first-in-class copper-protein-binding agent for oral therapy of Wilson's disease. In contrast to other decoppering agents such as trientine or D-penicillamine it acts by forming a tripartite complex with copper and albumin, thereby detoxifying excess liver and blood copper through biliary excretion. Preclinical animal experimentation with this drug was typically done with the alternative ammonium salt of tetrathiomolybdate, which is expected to have identical properties in terms of copper binding. Here, we comparatively analyzed the therapeutic efficacy of ALXN1840, D-penicillamine and trientine in lowering hepatic copper content in <i>Atp7b</i><sup>-/-</sup> mouse. Liver specimens were subjected to laser ablation inductively conductively plasma mass spectrometry and electron microscopic analysis. We found that ALXN1840 caused a massive increase of hepatic copper and molybdenum during early stages of therapy. Prolonged treatment with ALXN1840 reduced hepatic copper to an extent that was similar to that observed after administration of D-penicillamine and trientine. Electron microscopic analysis showed a significant increase of lysosomal electron-dense particles in the liver confirming the proposed excretory pathway of ALXN1840. Ultrastructural analysis of mice treated with dosages comparable to the bis-choline-tetrathiomolybdate dosage used in an ongoing phase III trial in Wilson's disease patients, as well as D-penicillamine and trientine, did not show relevant mitochondrial damage. In contrast, a high dose of ALXN1840 applied for four weeks triggered dramatic structural changes in mitochondria, which were notably characterized by the formation of holes with variable sizes. Although these experimental results may not be applicable to patients with Wilson's disease, the data suggests that ALXN1840 should be administered at low concentrations to prevent mitochondrial dysfunction and overload of hepatic excretory pathways.
Hydrogen-bonded liquid crystals built from hydrogen-bonding donors and acceptors. Infrared study on the stability of the hydrogen bond between carboxylic acid and pyridyl moieties (1993)

Abstract The stability of a hydrogen-bonded complex built through inter-molecular hydrogen bonding between carboxylic acid and pyridine fragments has been examined using infrared spectroscopy. Infrared spectra as a function of temperature have been recorded for the 1:1 complex of 4-hexyloxybenzoic acid and trans-4-propoxy-4′-stilbazole from the crystalline state to the isotropic state. A dependence of the stability of the hydrogen bond on molecular orientation is observed clearly in the infrared spectra. The spectra also suggest that the hydrogen bond is an unionized type with a double minimum potential energy.
Positive allosteric modulation of M1 muscarinic acetylcholine receptors suppresses lethal peripheral inflammation (P5082) (2013)

Abstract Peripheral inflammation can be regulated by activation of brain muscarinic acetylcholine receptor (mAChR)-dependent signaling functionally associated with a vagus-nerve mediated anti-inflammatory circuit (Proc Natl Acad Sci USA, 2006, 5219; Brain Behav Immun, 2009, 23:41). Here, we studied the specific role of the M1 mAChR subtype in this regulation by utilizing BQCA, a highly specific allosteric M1 mAChR activator that crosses the blood-brain barrier. Single drug (5,10 or 20 mg/kg, i.p) administration in mice 1h prior to endotoxin (8 mg/kg, i.p.) dose-dependently reduced serum and splenic TNF levels and significantly improved survival in mice as compared to vehicle-treated controls. Pharmacological blockade of brain mAChRs significantly abolished BQCA anti-inflammatory effects. Furthermore, BQCA (20 mg/kg, i.p.) significantly reduced serum and splenic TNF levels in wild type mice, but failed to alter TNF levels in M1 KO mice. Together these results indicate the anti-inflammatory role of increased functional activity of endogenous acetylcholine on the M1 mAChR by selective allosteric receptor activation. Our findings are of interest for further development of BQCA and other centrally-acting allosteric activators of the M1 mAChR as a novel class of experimental anti-inflammatory therapeutics.
Secure Data Management Technology (2020)

Abstract In this chapter, we introduce data anonymization techniques for several types of datasets. Data anonymity of anonymized datasets is an index for estimating the (maximum) reidentification risk from anonymized datasets and is generally defined as a quantitative index based on adversary models. The adversary models are implicitly defined according to the attributes in the datasets, use cases, and anonymization techniques. We first review existing anonymization techniques and the adversary models behind the data anonymity definitions for anonymization techniques; then, we propose a common anonymity definition and its adversary model, which is applicable to several types of anonymization techniques. Furthermore, some extensions of the definition, which is optimized for specific types of datasets, are presented in the chapter.
Perspectives on Infrastructure for Crowdsourcing (2011)

Human computation has gained a lot of interest lately as a paradigm for solving problems that computers can‟t do yet. Crowdsourcing marketplaces are showing that is possible to get tasks completed in time with a modest budget in a wide range of applications. However, the infrastructure that is currently available for supporting crowdsourcing tasks is very limited. There is non-trivial extra work that the experimenter has to do to get successful results. Consequently, the developer tends to spend more time dealing with the complexity and operational aspects of the task than on its design. Given the mix of different subareas of computer science that are potentially involved, defining and designing such platform presents a number of interesting problems. In this paper, I outline the rise of human computation, summarize the limitations of a popular platform, and present a perspective on the topic that can be viewed as a starting point to debate requirements for this new research area.
Approaches to the Azahelicene System: Synthesis and Spectroscopic Characterization of Some Diazapentahelicenes (2002)

The synthesis and spectroscopic characterization of some diazahelicenes is presented. The synthetic approach varies according to the location of the N-atoms; thus, three different synthetic pathways are used (Schemes 1–3). A description of UV/VIS and of fluorescence and phosphorescence emission is also reported. NMR Spectra show the importance of the distorted backbone of these molecules.
Scope and Impact of International Research in Human Pluripotent Stem Cells (2012)

In a recent study published in this journal it was claimed that the rate of publications from US-based authors in the human embryonic stem cell (hESC) research field was slowing or even declining from 2008 to 2010. It was assumed that this is the result of long-term effects of the Bush administration's funding policy for hESC research and the uncertain policy environment of recent years. In the present study, we analyzed a pool of more than 1,700 original hESC research papers published world-wide from 2007 to 2011. In contrast to the previous study, our results do not support the hypothesis of a decline in the productivity of US-based research but rather confirm a nearly unchanged leading position of US research in the hESC field with respect to both publication numbers and impact of research. Moreover, we analyzed about 500 papers reporting original research involving human induced pluripotent stem cells (hiPSCs) published through 2011 and found a dominant position of US research in this research field as well.
Nanoengineering DNA origami for lithography (2020)

DNA nanotechnology has shown great promise for nanopatterning applications thanks to the ability to nanoengineer rationally designed two and three-dimensional (3D) nano-objects of complex shapes with subnanometer precision and high degree of rigidity [1]. Recently, a self-assembled DNA origami allowing sub-10 nm pattern transfer into SiO2 has been demonstrated [2]. We report here a mechanistic study of a high resolution (10 nm) and high density (10 nm) DNA pattern transfer into a Si substrate. In order to exploit their full potential for lithographic application, the deterministic positioning of the DNA nanostructures on a predefined substrate is still a major challenge to overcome. In a second part of this paper, we present a hybrid nanopatterning process by combining locally chemically modified substrate by top-down technics with bottom-up self-assembly of DNA nanostructures in order to deterministically fix DNA origamis on the substrate. Chemical contrast is formed using conventional lithography in order to create DNA affine and adverse parts on the substrate. The pattern transfer of the DNA nanostructures in the inorganic under layer is demonstrated as well. Thus, DNA origami appears to be a promising emerging approach for the engineering of hard masks for patterning.
Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells. (1989)

The signals and cellular interactions required for hematopoietic stem-cell commitment to the T lineage are unknown, yet are central to understanding the early stages of normal T-cell development. To study the differentiative capacity of T-cell precursors, we isolated CD4-, CD8-, surface(s) CD3- thymocytes from postnatal human thymuses and determined their capacity to differentiate into lymphoid and nonlymphoid lineages in vitro. We found that CD4-, CD8-, sCD3- thymocytes, which differentiated in the presence of T-cell conditioned medium plus interleukin 2 into T cells expressing the gamma delta receptor for antigen, were capable of differentiating into myeloid or erythroid lineages in the presence of either 5637 bladder carcinoma cell line conditioned medium plus recombinant human erythropoietin or human thymic epithelial cell conditioned medium. Thymic epithelial cell conditioned medium was as effective as 5637 supernatant plus erythropoietin in inducing myeloerythroid differentiation in the CD4-, CD8-, sCD3- thymocytes. Sixty-eight +/- 14% of CD4-, CD8-, sCD3- thymocytes underwent nonlymphoid differentiation within 4 days in culture with 5637 supernatant plus erythropoietin. Twenty-six +/- 4% of freshly isolated CD4-, CD8-, sCD3- cells were CD34+, and clonal granulocyte/macrophage, granulocyte/erythrocyte/monocyte/megakaryocyte, and T-cell progenitors were found in both CD34+ and CD34- subsets of CD4-, CD8-, sCD3- thymocytes. Thus, cells within the human CD4-, CD8-, sCD3- thymocyte subset can give rise to gamma delta+ T cells as well as to cells of myeloerythroid lineages. Moreover, CD34+, CD4-, CD8-, sCD3- cells can give rise to clonal T-cell progenitors as well as to clonal myeloid progenitors.
New duality relating density perturbations in expanding and contracting Friedmann cosmologies (2004)

For a 4-dimensional spatially flat Friedmann-Robertson-Walker universe with a scalar field $\ensuremath{\varphi}(x),$ potential $V(\ensuremath{\varphi})$ and constant equation of state $w=p/\ensuremath{\rho},$ we show that an expanding solution characterized by $\ensuremath{\epsilon}=3(1+w)/2$ produces the same scalar perturbations as a contracting solution with $\stackrel{^}{\ensuremath{\epsilon}}=1/\ensuremath{\epsilon}.$ The same symmetry applies to both the dominant and subdominant scalar perturbation modes. This result admits a simple physical interpretation and generalizes to d spacetime dimensions if we define $\ensuremath{\epsilon}\ensuremath{\equiv}[(2d\ensuremath{-}5)+(d\ensuremath{-}1)w]/(d\ensuremath{-}2).$
Multiple Infeed Short Circuit Ratio &amp;#8211; Aspects Related to Multiple HVDC into One AC Network (2005)

The paper suggests an extension of the classical definition of Short Circuit Ratio and Effective Short Circuit Ratio to multiple infeed of HVDC transmission configuration. With such new indexes, which consider the interaction between converter stations, it is possible to predict low frequency resonances, dynamic overvoltages and risk for voltage and power instability at low value of the index, similar to single infeed configuration. In this paper it is also discussed other relevant issues related to integration of multiple HVDC links when the strength of the system is relatively low compared to the amount of power delivered by the HVDC links.
E112 Comparison of systemic and mucosal responses after DNA and protein co-immunization (2013)

Optimal protocols of DNA only vaccination elicit robust and broad humoral and cellular responses. These immune responses are able to significantly reduce peak and chronic viremia in macaques challenged with high dose SIVmac251. Despite the strong humoral responses, protein boost after DNA vaccination greatly increased Ab levels. Importantly, a co-immunization strategy of DNA&protein injected in the same muscle the same time induced highest and broadest humoral responses. Similar data were obtained using purified Env protein instead or viral particles. Inclusion of DNA in the vaccine promoted persistence of plasma antibody levels over long time (>2 yrs). DNA/protein vaccination induced: higher SIV Env-specific IgG in saliva; more responders with higher SIV Env-specific IgG in rectal fluids; higher and longer-lasting plasma bAb and Nab to homologous and heterologous Env. Vaccine-induced Ab responses against SIVsmE660 correlated with slower virus acquisition. Two of DNA&protein coimmunized macaques with high and persistent Ab responses showed sterilizing immunity after 14 exposures, while all controls were infected by 6 exposures. DNA&protein co-delivery increases the magnitude, quality and longevity of systemic and mucosal humoral immune responses in immunized rhesus macaques.
Correction: Frequent MAGE Mutations in Human Melanoma (2010)

Background: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype.
12 Evaluating the contribution of extracellular matrix invasion for killing of tumor cells by natural killer cells (2022)

<h3>Background</h3> Extracellular matrix (ECM) is a generic term for the diverse types of acellular structural component in tissues that play an important role in homeostasis. The ECM in solid tumors is greatly altered and can contribute to the modulation of immune cell function in the tumor microenvironment. Lymphocytes such as the cytotoxic natural killer and CD8+ T cells that are harnessed in immunotherapy can be regulated by the ECM. We hypothesized that matrigel layer presents a challenge for the NK cells and increasing the distance for invasion would delay the kinetics of tumor cell killing. Furthermore, invasion and killing of tumor targets would depend on their ability to remodel the matrix with matrix-metalloproteinases. <h3>Methods</h3> Briefly, increasing volumes (50–110 µL/well) of matrigel (6mg/mL) representing increasing distance for invasion was layered over MCF7-red target tumor cells expressing nuclear-localized mKate2 (red fluorescent protein). NK92 cells were seeded over the solidified matrigel layer at E:T of 3:1. Agilent eLive Green (1 µL/mL) was added to the wells. NK cell invasion and function was evaluated using impedance-based measurements of immune cell killing and live cell imaging data collected on xCELLigence RTCA eSight. <h3>Results</h3> Impedance increases with time as MCF7 target cells adhere and proliferate. The addition of NK92 cells results in a drop in impedance due to killing of the target cells. Total time taken for impedance levels to fall to levels at the time of NK92 addition increased progressively from 46h for 50 µL/well to 72 h for 110 µL/well. The eLive green stained NK cells and dead cells, but not healthy MCF7 targets. Consistent with impedance data, the loss of red fluorescence from target cells and increase in green fluorescence was progressively delayed with increasing volume of matrigel. A similar delay in kinetics was achieved with the broad spectrum MMP inhibitor GM6001 (2 µM and 10 µM), suggesting that MMPs played a role in the NK function. Interestingly, the NK-92 cells induce significant morphological changes in MCF7-red target cells prior to invading all the way through the Matrigel, suggesting an early distal effect. <h3>Conclusions</h3> The results suggest a role for effector functions of NK cells potentially involving cytokines, that is independent from invasion and/or ability to degrade the matrix, for the killing of susceptible target cells. The assay also demonstrates the potential for adapting the RTCA eSight platform to study various ECM interactions with immune cells.
Functional hard-coat for cartridge-free DVR-blue (2003)

Optical discs with larger storage capacity and higher data recording rates are required for the coming digital network society, for example, to realize non-linear editing and long term data archiving on broadcasting tasks. We have been developing a new phase change optical disc, which has much higher data recording rate of up to 140 Mbps (T. Kato et al, Tech. Dig. ISOM2001, pp. 200-201, 2001), based on the DVR system (/spl lambda/=405 nm, NA=0.85, cover layer thickness=100 /spl mu/m) (Y. Kuroda et al, 1999; M.J. Dekker et al, 2000; Y. Kasami et al, 2000). As a general rule, the smaller the laser spot size on the disc surface, the more sensitive the disc becomes to scratches or fingerprints on it. In such a system, the distance between the disc surface and objective lens (i.e. working distance) is very narrow due to a high NA. Therefore it is also feared that the objective lens hits the disc surface due to an external impact. To avoid these problems when the disc is taken out of a cartridge, we have developed a new hard-coat. The cartridge-free DVR-blue disc was expected to be accomplished by the following properties: (1) abrasion resistance; (2) scratch resistance; (3) water and oil repellency (low surface free energy). Among these properties, the abrasion resistance is considered to be the most important.
Structural elucidation of an -1,2-mannosidase resistant oligosaccharide produced in Pichia pastoris (2011)

The N-glycosylation pathway in Pichia pastoris has been humanized by the deletion of genes responsible for fungal-type glycosylation (high mannose) as well as the introduction of heterologous genes capable of forming human-like N-glycosylation. This results in a yeast host that is capable of expressing therapeutic glycoproteins. A thorough investigation was performed to examine whether glycoproteins expressed in glycoengineered P. pastoris strains may contain residual fungal-type high-mannose structures. In a pool of N-linked glycans enzymatically released by protein N-glycosidase from a reporter glycoprotein expressed in a developmental glycoengineered P. pastoris strain, an oligosaccharide with a mass consistent with a Hexose(9)GlcNAc(2) oligosaccharide was identified. When this structure was analyzed by a normal-phase high-performance liquid chromatography (HPLC), its retention time was identical to a Man(9)GlcNAc(2) standard. However, this Hexose(9)GlcNAc(2) oligosaccharide was found to be resistant to α-1,2-mannosidase as well as endomannosidase, which preferentially catabolizes endoplasmic reticulum oligosaccharides containing terminal α-linked glucose. To further characterize this oligosaccharide, we purified the Hexose(9)GlcNAc(2) oligosaccharide by HPLC and analyzed the structure by high-field one-dimensional (1D) and two-dimensional (2D) (1)H NMR (nuclear magnetic resonance) spectroscopy followed by structural elucidation by homonuclear and heteronuclear 1D and 2D (1)H and (13)C NMR spectroscopy. The results of these experiments lead to the identification of an oligosaccharide α-Man-(1 → 2)-β-Man-(1 → 2)-β-Man-(1 → 2)-α-Man-(1 → 2) moiety as part of a tri-antennary structure. The difference in enzymatic reactivity can be attributed to multiple β-linkages on the α-1,3 arm of the Man(9)GlcNAc(2) oligosaccharide.
Isolation and Characterization of cDNA Encoding Three Dehydrins Expressed During Coffea canephora (Robusta) Grain Development (2006)

cDNA sequences for three dehydrins and one LEA protein have been obtained and the expression of the associated genes has been determined in various tissues of arabica and robusta coffees. Because induction of dehydrin gene expression is associated with osmotic stress in other plants, the dehydrin sequences presented here will facilitate future studies on the induction and control of the osmotic stress response in coffee. The unique expression pattern observed for CcLEA1, and the expression of a related gene in other plants, suggests that this gene may play an important role in the development of grain endosperm tissue. Genomic DNA containing the grain-specific CcDH2 promoter region has been cloned. Sequence analysis indicates that this promoter contains several putative regulatory sites implicated in the control of both seed- and osmotic stress-specific gene expression. Thus, the CcDH2 promoter is likely to be a useful tool for basic studies on the control of gene expression during both grain maturation and osmotic stress in coffee.
Sensitivity and Specificity of Diagnostic Algorithms of Preoperative Anemia (2023)

We were able to show that the diagnostic anemia algorithm of the Institute for Blood Management, Gotha, Germany is superior to those of the Network for the Advancement of Transfusion Alternatives and the Society for the Advancement of Blood Management in its ability to detect the six common types of preoperative anemia in patients scheduled to undergo abdominal surgery, the presence of multiple types of anemias in a given patient, and its ability to detect rare anemias that have a clinical implication for management.
Frequency-domain optical imaging of absorption and scattering distributions by a Born iterative method (1997)

We presents a Born; iterative method, for reconstructing optical properties of turbid media by means of frequency-domain data. The approach is based on iterative solution of a linear perturbation equation, which is derived from the integral from of the Helmholtz wave equation for photon-density waves in each iteration the total field and the associated weight matrix are recalculated based on the previous reconstructed image. We then obtain a new estimate by solving the updated perturbation equation. The forward solution, also based on a Helmholtz equation, is obtained by a multigrid finite difference method. The inversion is carried out through a Tikhonov regularized optimization process by the conjugate gradient descent method. Using this method, we first reconstruct the distribution of the complex wave numbers in a test medium, from which the absorption and the scattering distributions are then derived. Simulation results with two-dimensional test media have shown that this method can yield quantitatively (in terms of coefficient valued) as well as qualitatively (in terms of object location and shape) accurate reconstructions of absorption and scattering distributions in cases in which the first-order Born approximation cannot work well. Both full-angle and limited-angle measurement schemes have been simulated to examine the effect of the location of detectors and sources. The robustness of the algorithm to noise has also been evaluated.