gebhart/patrepeval huggingface dataset:
Hierarchical Stochastic Neighbor Embedding (2016)

Abstract In recent years, dimensionality‐reduction techniques have been developed and are widely used for hypothesis generation in Exploratory Data Analysis. However, these techniques are confronted with overcoming the trade‐off between computation time and the quality of the provided dimensionality reduction. In this work, we address this limitation, by introducing Hierarchical Stochastic Neighbor Embedding (Hierarchical‐SNE). Using a hierarchical representation of the data, we incorporate the well‐known mantra of Overview‐First, Details‐On‐Demand in non‐linear dimensionality reduction. First, the analysis shows an embedding, that reveals only the dominant structures in the data (Overview). Then, by selecting structures that are visible in the overview, the user can filter the data and drill down in the hierarchy. While the user descends into the hierarchy, detailed visualizations of the high‐dimensional structures will lead to new insights. In this paper, we explain how Hierarchical‐SNE scales to the analysis of big datasets. In addition, we show its application potential in the visualization of Deep‐Learning architectures and the analysis of hyperspectral images.
Genetically engineered live-attenuated cytomegalovirus (CMV) vaccines improve pregnancy outcome in the guinea-pig model of congenital CMV infection (2008)

Methods The GPCMV genome was cloned as a BACmid in E. coli and used to regenerate a wild-type viral vaccine (wt), and a highly attenuated recombinant vaccine deleted of the gene encoding the dominant T-cell target, UL83 (pp65). Seronegative animals were immunized with a two-dose series of each vaccine (0and 3week schedule), or placebo. Following establishment of pregnancy, dams were challenged with salivary gland-passaged (SG) GPCMV (5×105 pfu) in the second trimester, and pregnancy outcomes were compared.
Polymorphic Cytochrome P450 Enzymes (CYPs) and Their Role in Personalized Therapy (2013)

The cytochrome P450 (CYP) enzymes are major players in drug metabolism. More than 2,000 mutations have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity. Therefore, CYPs play an important role in inter-individual drug response and their genetic variability should be factored into personalized medicine. To identify the most relevant polymorphisms in human CYPs, a text mining approach was used. We investigated their frequencies in different ethnic groups, the number of drugs that are metabolized by each CYP, the impact of CYP SNPs, as well as CYP expression patterns in different tissues. The most important polymorphic CYPs were found to be 1A2, 2D6, 2C9 and 2C19. Thirty-four common allele variants in Caucasians led to altered enzyme activity. To compare the relevant Caucasian SNPs with those of other ethnicities a search in 1,000 individual genomes was undertaken. We found 199 non-synonymous SNPs with frequencies over one percent in the 1,000 genomes, many of them not described so far. With knowledge of frequent mutations and their impact on CYP activities, it may be possible to predict patient response to certain drugs, as well as adverse side effects. With improved availability of genotyping, our data may provide a resource for an understanding of the effects of specific SNPs in CYPs, enabling the selection of a more personalized treatment regimen.
Electrodeposition of low stress gold for x-ray mask (1990)

In order to maintain the dimensional accuracy of an x-ray mask, the residual stress of the absorber must be kept low (in the low range of 108 dyn/cm2 ). The absorber material studied in this paper is pure gold electroplated from a proprietary plating solution. Stress of the gold deposits is measured by holographic interferometry of bending disk/beam experiments. The effects of temperature, current density, thickness, pH, and pulse plating on the stress of the gold are investigated. The aging behavior of the plating solution is also discussed. The stress of electroplated gold does not show a strong dependence on the current density (1–5 mA/cm2 ). However, aging of the plating solution changes the stress of the gold deposits, especially for those obtained at a current density of ∼1 mA/cm2. Pulse plating produces stress levels similar to those given by dc plating, over a wide range of on-current-density, on-time, and off-time. Moreover, the pH of the solution does not affect the stress of gold when the current density is greater than 1 mA/cm2. Hence a plating solution and process has been found that produces low stress gold (≤4×108 dyn/cm2) over a wide range of operating conditions and shows no adverse effects upon aging over an extended period of time.
Principles and Practices for Online Publishing (2001)

We wish to update our readers on steps being taken to enhance the Journal of Neuroscience in the near future. These steps will take advantage of developments in electronic journal publishing. Because this is a time of rapid change and uncertain future, it is appropriate to explain these steps from
Axonal effects of capsaicin: an electrophysiological study. (1986)

The effects of axonally applied capsaicin on the discharge activity and compound action potential of the cat vagus, saphenous and phrenic nerves and the cervical sympathetic trunk were studied under in vivo and in vitro conditions. Application of capsaicin (10(-4) M) to the vagus, saphenous and phrenic nerves resulted in the appearance of intense discharge activity which reached its maximum after 3-4 min and lasted for 15-20 min. Parallel with the increase in discharge activity, elicited by orthodromic activation induced by capsaicin, the amplitudes of the A delta and C components of an antidromically evoked compound action potential were significantly reduced. After the excitatory action of capsaicin vanished, an increase in the latency and duration and a decrease in the amplitudes of the components of the compound action potential were observed which might have led to the development of a local block of impulse propagation. These changes proved to be reversible after the removal of capsaicin from the nerve. Compound action potentials recorded from the saphenous or vagus nerves pretreated with capsaicin 3-5 days before the experiments failed to show any significant changes. It is concluded that upon direct axonal application capsaicin results in the excitation of both A delta and C fibres which is followed by a nonspecific but reversible blockade of impulse propagation. The possible significance of these transient effects of axonally applied capsaicin in term of the development of the highly specific functional impairment occurring a few days after perineural capsaicin treatment remains to be elucidated.
Immunotherapy: Bewitched, Bothered, and Bewildered No More (2004)

The field of immunotherapy holds clear promise not only for the development of new approaches to cancer and other diseases, but also for providing fundamental insight into the human immune response. In order for this promise to be realized, however, the scientific community must overcome an array of challenges. These challenges reflect not only the difficulties inherent in conducting investigations in human patients, but also difficulties created by the culture and practice of our own institutions, reward structure, and funding mechanisms. We suggest steps to be taken to reinvigorate basic research in human subjects as part of the mainstream of science.
New perspectives in mucosal immunity with emphasis on vaccine development. (1993)

In this review, we have purposely focused on five areas that are currently receiving extensive research attention and will be of major importance for development of mucosal and systemic immunity to oral vaccines. These five areas include the following: (1) helper T-cell (Th) subsets and cytokines for mucosal IgA responses; (2) Th1- and Th2-type subsets in regulation of mucosal IgA responses; (3) antigen uptake and presentation in the mucosal immune system; (4) the importance of memory in mucosal immunity to vaccines; and (5) the determination of whether oral immunization alone induces immunity in all mucosal effector tissues. It is now established that the mucosal immune system can be divided into discrete mucosal inductive sites where vaccines/antigens are encountered and taken up, processed, and presented to B and T cells, and separate areas where immune cells actually function (mucosal effector tissues). Further, through the help provided by Th cells and cytokines, the B cells respond to antigen and undergo expansion including memory cell formation. Following the migration of memory B cells to mucosal effector tissues, the cells rapidly develop into IgA plasma cells, and the prevalence of the latter cell type represents a major characteristic of mucosal effector tissues. It also appears that antigen-specific Th cells and perhaps even CD8+ cytotoxic T lymphocytes can make this circular journey (along with memory/activated B cells) from inductive to mucosal effector sites, and this is termed the common mucosal immune system (CMIS). The major implications of the CMIS for development of vaccines would include each of the five components that are discussed.
An Unusual Sulfur-Containing Diketopiperazine from the Bermudian Sponge Tedania ignis (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn Unusual Sulfur-Containing Diketopiperazine from the Bermudian Sponge Tedania ignisRhonda L. Dillman and John H. Cardellina II.Cite this: J. Nat. Prod. 1991, 54, 4, 1159–1161Publication Date (Print):July 1, 1991Publication History Published online1 July 2004Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/np50076a046https://doi.org/10.1021/np50076a046research-articleACS PublicationsRequest reuse permissionsArticle Views218Altmetric-Citations9LEARN 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
Targeted and nontargeted liposomes for in vivo transfer to rat liver cells of a plasmid containing the preproinsulin I gene. (1983)

A plasmid containing the rat preproinsulin I gene was entrapped in large liposomes and intravenously administered to rats. Four hours after inoculation, the livers were processed for the isolation of hepatocytes. Kupffer cells, and endothelial cells, DNA was purified, and the exogenous DNA was detected in the different cell DNA preparations by Southern blotting. By using liposomes consisting of phospholipids and cholesterol, Kupffer cells were shown to be, on a per cell basis, the primary target for gene incorporation. In an attempt to target the liposomes to other liver cells, a glycolipid, lactosylceramide, was included in the lipid bilayer of the liposomes; this resulted in a substantial increase in the proportion of the exogenous gene in the hepatocytes and mainly in the endothelial cells, with a simultaneous decrease of this proportion in the Kupffer cells. Thus, it is shown that inclusion of a specific glycolipid within the bilayer of the liposomes may direct the DNA-containing vesicles to specific cell types in the liver.
Real Time Face Detection and Facial Expression Recognition: Development and Applications to Human Computer Interaction. (2003)

Computer animated agents and robots bring a social dimension to human computer interaction and force us to think in new ways about how computers could be used in daily life. Face to face communication is a real-time process operating at a a time scale in the order of 40 milliseconds. The level of uncertainty at this time scale is considerable, making it necessary for humans and machines to rely on sensory rich perceptual primitives rather than slow symbolic inference processes. In this paper we present progress on one such perceptual primitive. The system automatically detects frontal faces in the video stream and codes them with respect to 7 dimensions in real time: neutral, anger, disgust, fear, joy, sadness, surprise. The face finder employs a cascade of feature detectors trained with boosting techniques [15, 2]. The expression recognizer receives image patches located by the face detector. A Gabor representation of the patch is formed and then processed by a bank of SVM classifiers. A novel combination of Adaboost and SVM's enhances performance. The system was tested on the Cohn-Kanade dataset of posed facial expressions [6]. The generalization performance to new subjects for a 7- way forced choice correct. Most interestingly the outputs of the classifier change smoothly as a function of time, providing a potentially valuable representation to code facial expression dynamics in a fully automatic and unobtrusive manner. The system has been deployed on a wide variety of platforms including Sony's Aibo pet robot, ATR's RoboVie, and CU animator, and is currently being evaluated for applications including automatic reading tutors, assessment of human-robot interaction.
The Development of Lung Disease in Cystic Fibrosis Pigs (2010)

The leading cause of death in cystic fibrosis (CF) patients is lung disease; yet despite enormous research efforts, its pathogenesis is not well understood. Because CF mice do not develop human-like airway disease, CF pigs were produced on the premise that they would offer insights into the pathogenesis of CF lung disease. But CF pigs develop severe intestinal blockage and often die shortly after birth. Now, a team of scientists report results from five CF pigs that lived for ~2 to 6 months; during this time, they developed some of the key features of human CF lung disease and revealed that infection precedes inflammation.
PDL1 Is Required for Peripheral Transplantation Tolerance and Protection from Chronic Allograft Rejection (2007)

The PD-1:PDL pathway plays an important role in regulating alloimmune responses but its role in transplantation tolerance is unknown. We investigated the role of PD-1:PDL costimulatory pathway in peripheral and a well established model of central transplantation tolerance. Early as well as delayed blockade of PDL1 but not PDL2 abrogated tolerance induced by CTLA4Ig in a fully MHC-mismatched cardiac allograft model. Accelerated rejection was associated with a significant increase in the frequency of IFN-gamma-producing alloreactive T cells and expansion of effector CD8(+) T cells in the periphery, and a decline in the percentage of Foxp3(+) graft infiltrating cells. Similarly, studies using PDL1/L2-deficient recipients confirmed the results with Ab blockade. Interestingly, while PDL1-deficient donor allografts were accepted by wild-type recipients treated with CTLA4Ig, the grafts developed severe chronic rejection and vasculopathy when compared with wild-type grafts. Finally, in a model of central tolerance induced by mixed allogeneic chimerism, engraftment was not abrogated by PDL1/L2 blockade. These novel data demonstrate the critical role of PDL1 for induction and maintenance of peripheral transplantation tolerance by its ability to alter the balance between pathogenic and regulatory T cells. Expression of PDL1 in donor tissue is critical for prevention of in situ graft pathology and chronic rejection.
Cultured Human Fibroblasts Express Constitutive IL-16 mRNA: Cytokine Induction of Active IL-16 Protein Synthesis Through a Caspase-3-Dependent Mechanism (2000)

Human fibroblasts can express numerous regulatory molecules that influence immune function. IL-16, a ligand for CD4, is a chemoattractant molecule expressed by lymphocytes, eosinophils, mast cells, and lung epithelium. It appears that the sole target for IL-16 is the CD4-bearing cell. Here we demonstrate that fibroblasts from several tissues can express IL-16 mRNA and protein as well as IL-16-dependent chemoattractant activity. The transcript is expressed abundantly under basal culture conditions as a 2.5-kb band on Northern analysis, similar to that observed in lymphocytes. IL-16 protein and activity are undetectable in fibroblast cultures under these same control conditions. However, when treated with proinflammatory cytokines such as IL-1beta, they express very high levels of IL-16 protein and chemoattractant activity, a substantial component of which can be blocked with IL-16-neutralizing Abs. The amount of IL-16 protein released into the medium is 3- to 4-fold greater, on a per cell basis, than that observed in lymphocytes. The induction of IL-16 protein by IL-1beta can be attenuated with specific inhibition of caspase-3, which could be detected in IL-1beta-treated fibroblasts. IL-1beta also induces RANTES mRNA, protein, and activity, and most of the chemoattractant activity released from fibroblasts not derived from IL-16 can be attributed to RANTES. Human fibroblasts appear to be an important source of IL-16 and through expression of this molecule may have key roles in the recruitment of CD4+ cells to sites of inflammation. IL-16 expression and the mechanism involved in its regulation appear to be cell type specific.
Biochemical and genetic characterization of enterocin P, a novel sec-dependent bacteriocin from Enterococcus faecium P13 with a broad antimicrobial spectrum (1997)

Enterocin P is a new bacteriocin produced by Enterococcus faecium P13 isolated from a Spanish dry-fermented sausage. Enterocin P inhibited most of tested spoilage and food-borne gram-positive pathogenic bacteria, such as Listeria monocytogenes, Staphylococcus aureus, Clostridium perfringens, and Clostridium botulinum. Enterocin P is produced during growth in MRS broth from 16 to 45 degrees C; it is heat resistant (60 min at 100 degrees C; 15 min at 121 degrees C) and can withstand exposure to pH between 2.0 and 11.0, freeze-thawing, lyophilization, and long-term storage at 4 and -20 degrees C. The bacteriocin was purified to homogeneity by ammonium sulfate precipitation, gel filtration, cation-exchange, hydrophobic-interaction, and reverse-phase liquid chromatography. The sequence of 43 amino acids of the N terminus was obtained by Edman degradation. DNA sequencing analysis of a 755-bp region revealed the presence of two consecutive open reading frames (ORFs). The first ORF encodes a 71-amino-acid protein containing a hydrophobic N-terminal sec-dependent leader sequence of 27 amino acids followed by the amino acid sequence corresponding to the purified and sequenced enterocin P. The bacteriocin is apparently synthesized as a prepeptide that is cleaved immediately after the Val-Asp-Ala residues (positions -3 to -1), resulting in the mature bacteriocin consisting of 44 amino acids, and with a theoretical molecular weight of 4,493. A second ORF, encoding a putative immunity protein composed of 88 amino acids with a calculated molecular weight of 9,886, was found immediately downstream of the enterocin P structural gene. Enterocin P shows a strong antilisterial activity and has the consensus sequence found in the pediocin-like bacteriocins; however, enterocin P is processed and secreted by the sec-dependent pathway.
Simulations of nanopore formation and phosphatidylserine externalization in lipid membranes subjected to a high-intensity, ultrashort electric pulse (2005)

A combined MD simulator and time dependent Laplace solver are used to analyze the electrically driven phosphatidylserine externalization process in cells. Time dependent details of nanopore formation at cell membranes in response to a high-intensity (100 kV/cm), ultrashort (10 ns) electric pulse are also probed. Our results show that nanosized pores could typically be formed within about 5 ns. These predictions are in very good agreement with recent experimental data. It is also demonstrated that defect formation and PS externalization in membranes should begin on the anode side. Finally, the simulations confirm that PS externalization is a nanopore facilitated event, rather than the result of molecular translocation across the trans-membrane energy barrier.
Aminomethylation of Ferrocene to Form N,N-Dimethylaminomethylferrocene and Its Conversion to the Corresponding Alcohol and Aldehyde1 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAminomethylation of Ferrocene to Form N,N-Dimethylaminomethylferrocene and Its Conversion to the Corresponding Alcohol and Aldehyde1JACQUE K. LINDSAY and CHARLES R. HAUSERCite this: J. Org. Chem. 1957, 22, 4, 355–358Publication Date (Print):April 1, 1957Publication History Published online1 May 2002Published inissue 1 April 1957https://doi.org/10.1021/jo01355a001RIGHTS & PERMISSIONSArticle Views1727Altmetric-Citations194LEARN 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 (473 KB) Get e-Alerts Get e-Alerts
A library of chemically defined human N-glycans synthesized from microbial oligosaccharide precursors (2017)

Synthesis of homogenous glycans in quantitative yields represents a major bottleneck to the production of molecular tools for glycoscience, such as glycan microarrays, affinity resins, and reference standards. Here, we describe a combined biological/enzymatic synthesis that is capable of efficiently converting microbially-derived precursor oligosaccharides into structurally uniform human-type N-glycans. Unlike starting material obtained by chemical synthesis or direct isolation from natural sources, which can be time consuming and costly to generate, our approach involves precursors derived from renewable sources including wild-type Saccharomyces cerevisiae glycoproteins and lipid-linked oligosaccharides from glycoengineered Escherichia coli. Following deglycosylation of these biosynthetic precursors, the resulting microbial oligosaccharides are subjected to a greatly simplified purification scheme followed by structural remodeling using commercially available and recombinantly produced glycosyltransferases including key N-acetylglucosaminyltransferases (e.g., GnTI, GnTII, and GnTIV) involved in early remodeling of glycans in the mammalian glycosylation pathway. Using this approach, preparative quantities of hybrid and complex-type N-glycans including asymmetric multi-antennary structures were generated and subsequently used to develop a glycan microarray for high-throughput, fluorescence-based screening of glycan-binding proteins. Taken together, these results confirm our combined synthesis strategy as a new, user-friendly route for supplying chemically defined human glycans simply by combining biosynthetically-derived precursors with enzymatic remodeling.