gebhart/patrepeval huggingface dataset:
Sequencing Oligonucleotides by Enrichment of Coupling Failures Using Matrix‐Assisted Laser Desorption/Ionization Time‐of‐Flight Mass Spectrometry (2005)

A technique for sequencing oligonucleotides using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is described. Coupling failures are extracted from the full-length 5'-O-DMTr-oligonucleotide in a crude synthesis using C18 purification cartridges. Enhanced signal and resolution of the failure ions are demonstrated during MALDI-TOF analysis. Sequencing information is confirmed by the mass difference between coupling failures to identify a particular base or structural modification. This procedure eliminates difficulties associated with other mass spectrometric techniques, such as interpretation of data, oligonucleotide length, and backbone, sugar or terminal alterations. An example of sequencing a 16-mer composed of deoxyribonucleotides, 2'-O-methylribonucleotides, and a non-nucleosidic linker is reported.
Fluorogenic and chromogenic substrates used in bacterial diagnostics (1991)

Methods based on the application of chromogenic and fluorogenic substrates enable specific and rapid detection of a variety of bacterial enzymatic activities. By using these techniques, enzymatic reactions can be examined simultaneously or individually, either directly on the isolation plate or in cell suspensions. For this purpose, various testing principles and test kits for clinical and food microbiology have been introduced successfully during the last few years. In this paper we present a survey of different enzymes of microbial origin that are utilized for microbiological identification and differentiation and the corresponding methods. Particular emphasis is given to the examination of Escherichia coli and the description of the different techniques as used in routine analysis.
Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference (2004)

Gene expression analysis implicates an increasing number of novel genes in the brain as potential targets for the treatment of neurological and psychiatric disorders. Frequently, these genes are ubiquitously expressed in the brain and, thus, may contribute to a pathophysiological state through actions in several brain nuclei. Current strategies employing genetically modified animals for in vivo validation of such targets are time-consuming and often limited by developmental adaptations. Somatic gene manipulation using viral-mediated RNA interference (RNAi) has emerged recently, although restricting the target validation to specific brain nuclei. We investigated whether nonviral infusion of short interfering RNA (siRNA) into the ventricular system would enable a sequence-specific gene knockdown. The temporality and extent of siRNA-induced down-regulation were analyzed by targeting a transgene, EGFP, in mice overexpressing EGFP. Extensive knockdown of EGFP was observed, especially in regions adjacent or dorsoventrally and mediolaterally distant to the infusion site (dorsal third ventricle), with lesser knockdown in more distal regions. We challenged our RNAi approach to generate a specific knockdown of an endogenous gene, encoding the dopamine transporter (DAT) in regions (ventral midbrain) far distal to the infusion site. DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein in the brain and also elicited a temporal hyperlocomotor response similar to that (but delayed) obtained upon infusion of GBR-12909, a pharmacologically selective DAT inhibitor. Application of this nonviral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions.
A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants (1999)

Posttranscriptional gene silencing (PTGS) is a nucleotide sequence-specific defense mechanism that can target both cellular and viral mRNAs. Here, three types of transgene-induced PTGS and one example of virus-induced PTGS were analyzed in plants. In each case, antisense RNA complementary to the targeted mRNA was detected. These RNA molecules were of a uniform length, estimated at 25 nucleotides, and their accumulation required either transgene sense transcription or RNA virus replication. Thus, the 25-nucleotide antisense RNA is likely synthesized from an RNA template and may represent the specificity determinant of PTGS.
Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG (1991)

Cellular receptors for IgG (Fc gamma R) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human Fc gamma RI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates Fc gamma RI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in Fc gamma RI recognition. We have also mapped an interaction site for Fc gamma RII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in Fc gamma RII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human Fc gamma RI and Fc gamma RII.
Capacitative calcium entry: from concept to molecules (2009)

Rapid to moderately rapid changes in intracellular Ca2+ concentration, or Ca2+ signals, control a variety of critical cellular functions in the immune system. These signals are comprised of Ca2+ release from intracellular stores coordinated with Ca2+ influx across the plasma membrane. The most common mechanisms by which these two modes of signaling occur is through inositol 1,4,5-trisphosphate (IP3)-induced release of Ca2+ from the endoplasmic reticulum (ER) and store-operated Ca2+ entry across the plasma membrane. The latter process was postulated over 20 years ago, and in just the past few years, the key molecular players have been discovered: STIM proteins serve as sensors of Ca2+ within the ER which communicate with and activate plasma membrane store-operated channels composed of Orai subunits. The process of store-operated Ca2+ entry provides support for oscillating Ca2+ signals from the ER and also provides direct activator Ca2+ that signals to a variety of downstream effectors.
Plexins, Semaphorins, and Scatter Factor Receptors: A Common Root for Cell Guidance Signals? (1999)

Semaphorins, the plexin family of semaphorin receptors, and scatter factor receptors share evolutionarily conserved protein modules, such as the semaphorin domain and Met Related Sequences (MRS). All these proteins also have in common a role in mediating cell guidance cues. During development, scatter factor receptors control cell migration, epithelial tubulogenesis, and neurite extension. Semaphorins and their receptors are known signals for axon guidance; they are also suspected to regulate developmental processes involving cell migration and morphogenesis, and have been implicated in immune function and tumor progression. Scatter factors and secreted semaphorins are diffusible ligands, whereas membrane-bound semaphorins signal by cell-cell interaction. Cell guidance control by semaphorins requires plexins, alone or in a receptor complex with neuropilins. Semaphorins, besides their role in axon guidance, are expected to have multiple functions in morphogenesis and tissue remodeling by mediating cell-repelling cues through plexin receptors.
Mixed Duopoly Under Vertical Differentiation (1994)

In this paper we study a vertically differentiated duopoly market with a profit maximizing firm (private firm) and a total surplus maximizing firm (public firm). The technological conditions are assumed identical for both firms and are described by unit costs which are constant with respect to quantity, though increasing in quality. No specific form is given to the relation between unit costs and quality. We prove that the socially optimal solution can be sustained as a market outcome by using a public firm as a market agent. We also provide conditions on the constant unit cost function under which every market outcome is a social optimum.
Localization of Epstein-Barr Viral Genomes in Angiocentric Immunoproliferative Lesions (1992)

Epstein-Barr virus has been demonstrated in angiocentric immunoproliferative lesions. However, these studies, which have used the polymerase chain reaction technique or Southern blot analysis, have not revealed the identity of the cell population harboring the virus. To address this issue, we analyzed 12 angiocentric immunoproliferative lesions (14 biopsy specimens) for Epstein-Barr virus RNA using a sensitive and specific in situ hybridization method. Epstein-Barr virus RNA was detected in five of 12 cases. Each positive lesion was a high-grade angiocentric immunoproliferative lesion (i.e., angiocentric lymphoma) in which Epstein-Barr virus was identified in numerous cells. Furthermore, the Epstein-Barr virus-positive cells were often larger than normal lymphocytes and thus were most likely the malignant cells. Double-labeling immunohistochemistry/in situ hybridization studies revealed that the majority of Epstein-Barr virus-positive cells were CD43-positive and CD20-negative, consistent with T-cell lineage. The remaining seven cases, all grade I or II angiocentric immunoproliferative lesions, were either completely negative (four cases) or had only rare to occasional Epstein-Barr virus-positive cells (three cases). The results obtained with the polymerase chain reaction and Southern blot hybridization studies generally confirmed those obtained with in situ hybridization. We conclude that Epstein-Barr virus is frequently associated with angiocentric immunoproliferative lesions, particularly within high-grade lesions, in which the virus is probably present within the neoplastic cells. These findings also suggest that Epstein-Barr virus may be involved in the transformation of low-grade angiocentric immunoproliferative lesions to histologically unequivocal angiocentric lymphomas.
Activation of the mitogen‐activated protein kinase pathway through p75NTR: A common mechanism for the neurotrophin family (2003)

Neurotrophins interact with two distinct classes of cell-surface receptors, the Trk receptor tyrosine kinase family and the common neurotrophin receptor p75(NTR). For many years, the biological role of p75(NTR) remained obscure, being relegated to modulating Trk binding of neurotrophins. Recently, the importance of p75(NTR) as a signaling receptor in itself has become increasingly clear. The signals initiated by p75(NTR) are likely to be as complex as those for the Trk family and probably depend on the cell system in which such signaling is being studied. In this study, all members of the neurotrophin family were demonstrated to be capable of stimulating p75(NTR)-mediated activation of the mitogen-activated protein kinase (MAPK) family (ERK1,2). This activation is rapid and transient, peaking at 5-15 min, depending on the cell system. The classical MAPK cascade consists of the reaction series Ras-Raf-MEK-MAPK. The p75(NTR)-induced MAPK activation is MEK dependent but Raf independent. This result implies that neurotrophin activation of p75(NTR) results in some cascade (as yet unknown) that bypasses Raf and converges on MEK to result in activation of MAPK. This activated MAPK is then able to translocate to the nucleus. The effect of this MAPK activation on cell survival is dependent on cell type. These results support the concept that signaling from the p75(NTR) receptor is more diverse and extensive than previously believed.
Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck (2004)

CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy. The expression does not seem to have prognostic significance.
Synthesis of orally active small-molecule gonadotropin-releasing hormone antagonists. (2004)

Recent success in the search for orally active gonadotropin-releasing hormone antagonists for the treatment of sex hormone-related diseases, such as endometriosis, uterine fibroids and prostate cancer, has resulted in the discovery of non-peptide compounds from several different chemical classes. At least two such compounds have advanced to the clinic for testing in humans, while multiple series of compounds have demonstrated oral activity in animal studies. This review covers the basic biological activity and the syntheses of these compounds, focusing on progress made over the past year.
In Vitro Induction of Mucosa-Type Dendritic Cells by All- Trans Retinoic Acid (2007)

Efficient induction of mucosal immunity usually employs nasal or oral vaccination while parenteral immunization generally is ineffective at generating mucosal immune responses. This relates to the unique ability of resident mucosal dendritic cells (DC) to induce IgA switching and to imprint mucosa-specific homing receptors on lymphocytes. Based on the well-established plasticity of the DC system, this study sought to investigate whether peripheral DC could be modulated toward "mucosa-type" DC by treatment with immunomodulatory, and therefore potentially adjuvant-like, factors. In this study, we show that monocyte-derived DCs pretreated with the vitamin A derivative all-trans retinoic acid (RA) indeed acquired several attributes characteristic of mucosal DC: secretion of TGF-beta and IL-6 and the capacity to augment mucosal homing receptor expression and IgA responses in cocultured lymphocytes. Addition of a TGF-beta-neutralizing Ab to cocultures significantly inhibited alpha4beta7 integrin, but not CCR9 mRNA expression by the lymphocytes. Both alpha4beta7 integrin and CCR9 mRNA expression, but not IgA production, were suppressed in the presence of a RA receptor antagonist. None of the observed effects on the lymphocytes were influenced by citral, a retinal dehydrogenase inhibitor, arguing against a role for de novo-synthesized RA. Collectively, our findings identified a novel role for RA as a mucosal immune modulator targeting DC. Our results further demonstrate that DC can act as efficient carriers of RA at least in vitro. Consequently, RA targeting of DC shows potential for promoting vaccine-induced mucosal immune responses via a parenteral route of immunization.
Definition of treatment goals for moderate to severe psoriasis: a European consensus (2010)

Patients with moderate to severe psoriasis are undertreated. To solve this persistent problem, the consensus programme was performed to define goals for treatment of plaque psoriasis with systemic therapy and to improve patient care. An expert consensus meeting and a collaborative Delphi procedure were carried out. Nineteen dermatologists from different European countries met for a face-to-face discussion and defined items through a four-round Delphi process. Severity of plaque psoriasis was graded into mild and moderate to severe disease. Mild disease was defined as body surface area (BSA) ≤10 and psoriasis area and severity index (PASI) ≤10 and dermatology life quality index (DLQI) ≤10 and moderate to severe psoriasis as (BSA > 10 or PASI > 10) and DLQI > 10. Special clinical situations may change mild psoriasis to moderate to severe including involvement of visible areas or severe nail involvement. For systemic therapy of plaque psoriasis two treatment phases were defined: (1) induction phase as the treatment period until week 16; however, depending on the type of drug and dose regimen used, this phase may be extended until week 24 and (2) maintenance phase for all drugs was defined as the treatment period after the induction phase. For the definition of treatment goals in plaque psoriasis, the change of PASI from baseline until the time of evaluation (ΔPASI) and the absolute DLQI were used. After induction and during maintenance therapy, treatment can be continued if reduction in PASI is ≥75%. The treatment regimen should be modified if improvement of PASI is <50%. In a situation where the therapeutic response improved ≥50% but <75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is ≤5. This programme defines the severity of plaque psoriasis for the first time using a formal consensus of 19 European experts. In addition, treatment goals for moderate to severe disease were established. Implementation of treatment goals in the daily management of psoriasis will improve patient care and mitigate the problem of undertreatment. It is planned to evaluate the implementation of these treatment goals in a subsequent programme involving patients and physicians.
Galactosylated N-2-Hydroxypropyl Methacrylamide-b-N-3-Guanidinopropyl Methacrylamide Block Copolymers as Hepatocyte-Targeting Gene Carriers (2011)

As alternatives of viral and cationic lipid gene carriers, cationic polymer-based vectors may provide flexible chemistry for the attachment of targeting moieties. In this report, galactosylated N-2-hydroxypropyl methacrylamide-b-N-3-guanidinopropyl methacrylamide block copolymers (galactosylated HPMA-b-GPMA block copolymers, or abbreviated as GHG) were prepared in order to develop hepatocyte targeting gene transfection carriers. The block copolymers were synthesized by aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization of N-2-hydroxypropyl methacrylamide (HPMA) and N-3-aminopropyl methacrylamide (APMA), followed by galactosylation and guanidinylation. The molecular weight of GHG copolymers determined by static light scattering method was in the range from 48 600 to 76 240 g/mol. In addition, the galactose content in the GPMA block in the copolymers was determined to be 6.5-8.0 mol % according to the sulfuric acid method. The GHG copolymers complexed completely with plasmid DNA (pDNA) to show positive zeta-potential values with diameter 100-250 nm from charge ratio of 4, which demonstrated the excellent DNA condensing ability of guanidino groups. Furthermore, the MTT assay data of GHG/pDNA complexes on HepG2 cells and HeLa cells indicated that GHG copolymers had significantly lower cytotoxicity than PEI. In addition, the copolymers with GPMA component from 30.23% showed higher transfection efficiency than PEI at charge ratio of 12 in HepG2 cells. The result revealed that the conjugation of galactose groups in the copolymers brought asialoglycoprotein-receptor (ASGP-R) mediated transfection. The employing of HPMA component decreased the aggregation of protein in transfection presence of serum. The GHG copolymers combined the advantages of galactose moieties, guanidino groups, and HPMA component might show potential in safe hepatocyte targeting gene therapy.
Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities (2008)

Tumor regressions have been observed in a small proportion of melanoma patients vaccinated with a MAGE-A3 peptide presented by HLA-A1, administered as peptide, ALVAC canarypox virus containing a MAGE-A3 minigene, or peptide-pulsed dendritic cells (DC). There was a correlation between tumor regression and the detection of anti-MAGE-3.A1 CTL responses. These responses were monoclonal and often of a very low magnitude after vaccination with peptide or ALVAC, and usually polyclonal and of a higher magnitude after DC vaccination. These results suggested that, at least in some patients, surprisingly few anti-MAGE-3.A1 T-cells could initiate a tumor regression process. To understand the role of these T cells, we carried out a functional analysis of anti-MAGE-3.A1 CTL clones derived from vaccinated patients who displayed tumor regression. The functional avidities of these CTL clones, evaluated in lysis assays, were surprisingly low, suggesting that high avidity was not part of the putative capability of these CTL to trigger tumor rejection. Most anti-MAGE-3.A1 CTL clones obtained after DC vaccination, but not after peptide or ALVAC vaccination, produced interleukin 10. Transcript profiling confirmed these results and indicated that approximately 20 genes, including CD40L, prostaglandin D2 synthase, granzyme K, and granzyme H, were highly differentially expressed between the anti-MAGE-3.A1 CTL clones derived from patients vaccinated with either peptide-ALVAC or peptide-pulsed DC. These results indicate that the modality of vaccination with a tumor-specific antigen influences the differentiation pathway of the antivaccine CD8 T-cells, which may have an effect on their capacity to trigger a tumor rejection response.
General Preparation of Functionalizedo-Nitroarylmagnesium Halides through an Iodine-Magnesium Exchange (2002)

Highly functionalized aryl Grignard reagents with an ortho-nitro substituent have been synthesized from 2-iodonitroaryl compounds through an I–Mg exchange reaction with PhMgCl or mesityl magnesium bromide (see scheme). These reagents are stable (T<−20°C for several hours) and undergo various cross-coupling reactions in the presence of Cu or Pd catalysts (dba = trans,trans-dibenzylideneacetone; tfp = tri-o-furylphosphane).
The Paradox of Disease Prevention (2013)

Prevention of disease is often difficult to put into practice. Among the obstacles: the success of prevention is invisible, lacks drama, often requires persistent behavior change, and may be long delayed; statistical lives have little emotional effect, and benefits often do not accrue to the payer; avoidable harm is accepted as normal, preventive advice may be inconsistent, and bias against errors of commission may deter action; prevention is expected to produce a net financial return, whereas treatment is expected only to be worth its cost; and commercial interests as well as personal, religious, or cultural beliefs may conflict with disease prevention. Six strategies can help overcome these obstacles: (1) Pay for preventive services. (2) Make prevention financially rewarding for individuals and families. (3) Involve employers to promote health in the workplace and provide incentives to employees to maintain healthy practices. (4) Reengineer products and systems to make prevention simpler, lower in cost, and less dependent on individual action. (5) Use policy to reinforce choices that favor prevention. (6) Use multiple media channels to educate, elicit health-promoting behavior, and strengthen healthy habits. Prevention of disease will succeed over time insofar as it can be embedded in a culture of health.
Constitutive expression of a fruit phytoene synthase gene in transgenic tomatoes causes dwarfism by redirecting metabolites from the gibberellin pathway (1995)

Tomato plants transformed with a copy of the fruit‐expressed phytoene synthase cDNA under control of the CaMV 35S promoter showed ectopic production of carotenoids. High expressers were reduced in stature. The dwarf character was inherited with an inverse relationship between expression of phytoene synthase and plant height. Severely affected plants also showed reduced chlorophyll content in young leaves. These dwarfs showed a 30‐fold reduction in levels of gibberellin A 1 (GA 1 ) and growth was partially restored by treatment with exogenous GA 3 . Qualitative and quantitative changes in carotenoids were also found. It is proposed that the dwarf phenotype results from the over‐production of phytoene synthase, which converts geranylgeranyl diphosphate to phytoene and thereby diverts this intermediate away from the gibberellin (GA) and phytol biosynthetic pathways.