gebhart/patrepeval huggingface dataset:
Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice (2008)

Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-gamma+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-gamma+ CD8+ T cells (3.9+/-1% naïve vs. 3.6+/-1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40+/-10 reciprocal dilution, both groups). The number of INF-gamma+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146+/-14, naïve vs. 120+/-16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by approximately 25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-gamma+ CD8+ T cells 10 days after administration (0.3+/-0.3% PEG vs. 1.7+/-0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.
Performance of Linear Extrapolation Methods for Virtual Sound Field Navigation (2020)

Performance errors are characterized for two representative linear extrapolation methods for virtual navigation of higher-order ambisonics sound fields. For such methods, navigation is theoretically restricted to within the so-called region of validity, which spherically extends from the recording ambisonics microphone to its nearest source, but the precise consequences of violating that restriction have not been previously established. To that end, the errors introduced by each method are objectively evaluated, in terms of metrics for sound level, spectral coloration, source localization, and diffuseness, through numerical simulations over a range of valid and invalid conditions. Under valid conditions, results show that the first method, based on translating along plane-waves, accurately reproduces both the level and localization of a source, whereas the second method, based on ambisonics translation coefficients, incurs significant errors in both level and spectral content that increase steadily with translation distance. Under invalid conditions, two common features of the performance of both methods are identified: significant localization errors are introduced and the reproduced level is too low. It is argued that these penalties are inherent to all methods that are bound by the region of validity restriction, including all linear extrapolation methods.
Self-peptides from four HLA-DR alleles share hydrophobic anchor residues near the NH2-terminal including proline as a stop signal for trimming. (1993)

Naturally processed MHC class II-associated peptides proved to be heterogeneous in size, varying from 13 to 25 amino acids. Truncation variants suggested sequence motifs that afford the amino termini to be shifted for obtaining an alignment: a 9- to 11-residue core region that is bordered by primary anchor residues is surrounded by extra sequences of variable lengths and hitherto unknown functions. Herein we present bulk sequencing analyses of self-peptides from four HLA-DR alleles and HLA-DQw7 clearly showing that the length of most of the NH2-terminal preanchor sequence is limited to 1 to 3 residues. Most strikingly, proline is the dominant residue reappearing at positions 2 and 3 in any allele. Proline revealed to function as a stop signal for NH2-terminal trimming as well as a secondary anchor: crude cytosolic and endosomal peptide fractions could be processed by aminopeptidases in vitro, whereupon DR1 binding peptides with increased affinity were generated. In addition, aminopeptidase treatment of DR1: self-peptide complexes implied that proline together with sterical constraints of the MHC molecule do protect the peptides' NH2-termini from further processing, whereas their COOH-termini were accessible to cathepsin B processing. Finally, bulk sequencing profiles contained signals from further putative anchor residues clustering in the NH2-terminal region:tyrosine, phenylalanine, leucine, isoleucine, and valine are enriched at positions 2 to 4 in DR1, DR5, and DR6, however, at positions 4 to 6 in DR3. Isotype-specificity is demonstrated by DQw7 displaying glutamine and asparagine at position 2. Obviously, the degenerate occurrence of aromatic or aliphatic side chains close to the NH2-terminal guarantees for essential interactions with a hydrophobic pocket of the investigated DR molecules. Most probably, this pocket is located in the nonpolymorphic DR alpha-chain rationalizing previous findings of promiscuous peptide binding to different DR alleles.
CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells (2015)

Glioblastoma (GB) remains the most aggressive primary brain malignancy. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered natural killer (NK) cells to treat GB has not been explored. Tumors from approximately 50% of GB patients express wild-type EGFR (wtEGFR) and in fewer cases express both wtEGFR and the mutant form EGFRvIII; however, previously reported CAR T cell studies only focus on targeting EGFRvIII. Here we explore whether both wtEGFR and EGFRvIII can be effectively targeted by CAR-redirected NK cells to treat GB. We transduced human NK cell lines NK-92 and NKL, and primary NK cells with a lentiviral construct harboring a second generation CAR targeting both wtEGFR and EGFRvIII and evaluated the anti-GB efficacy of EGFR-CAR-modified NK cells. EGFR-CAR-engineered NK cells displayed enhanced cytolytic capability and IFN-γ production when co-cultured with GB cells or patient-derived GB stem cells in an EGFR-dependent manner. In two orthotopic GB xenograft mouse models, intracranial administration of NK-92-EGFR-CAR cells resulted in efficient suppression of tumor growth and significantly prolonged the tumor-bearing mice survival. These findings support intracranial administration of NK-92-EGFR-CAR cells represents a promising clinical strategy to treat GB.
An Application of Related Term Extraction to Transliteration into Chinese (2010)

外国語を翻字するときに，日本語や韓国語ではカタカナやハングルなどの表音文字を用いるのに対して，中国語では漢字を用いる．しかし，漢字は表意文字であるため，発音が同じでも漢字によって意味や印象は異なる可能性がある．この問題を解消するために，ユーザが与えた関連語に基づいて翻字に使用する漢字を選択する手法がある．しかしユーザの負担が大きいため，本研究は，翻字対象の関連語を World Wide Web から自動的に抽出し，中国語への翻字に使用する手法を提案する．評価実験によって提案手法の有効性を示す．
Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice (2002)

Genomic imprinting is regulated by differential methylation of the paternal and maternal genome. However, it remains unknown how parental imprinting is established during gametogenesis. In this study, we demonstrate that Dnmt3L, a protein sharing homology with DNA methyltransferases, Dnmt3a and Dnmt3b, but lacking enzymatic activity, is essential for the establishment of maternal methylation imprints and appropriate expression of maternally imprinted genes. We also show that Dnmt3L interacts with Dnmt3a and Dnmt3b and co-localizes with these enzymes in the nuclei of transfected cells, suggesting that Dnmt3L may regulate genomic imprinting via the Dnmt3 family enzymes. Consistent with this model, we show that [Dnmt3a(-/-), Dnmt3b(+/-)] mice also fail to establish maternal methylation imprints. In addition, both Dnmt3a and Dnmt3L are required for spermatogenesis. Together, our findings suggest that Dnmt3L may cooperate with Dnmt3 family methyltransferases to carry out de novo methylation of maternally imprinted genes in oocytes.
AVALIAÇÃO DO EQUILÍBRIO ESTÁTICO EM INDIVÍDUOS COM ESTRABISMO (2015)

Introducao : A alteracao do equilibrio em individuos com comprometimento visual, a exemplo do estrabismo, tem sido alvo de diversos estudos nas duas ultimas decadas, uma vez que a visao desempenha um importante papel na manutencao da postura e do equilibrio, sendo a fonte de entrada principal de informacoes para a manutencao do equilibrio estatico. Objetivo : Avaliar o equilibrio estatico em individuos estrabicos. Metodologia : Estudo observacional transversal quantitativa, composto de 34 voluntarios divididos em dois grupos: Grupo Estudo, 17 individuos estrabicos, e Grupo Controle, 17 individuos de visao normal. A avaliacao do equilibrio estatico foi realizada atraves da plataforma estabilometria, primeiro com olhos abertos e, em seguida fechados, na posicao bipede estatica durante 52 segundos em cada momento. Foram estudadas as variaveis: velocidade media de oscilacao, deslocamento ântero-posterior (A/P) e latero-lateral, em milimetros por segundos (mm/s), e a superficie eliptica, em milimetro ao quadrado (mm²). Utilizou-se o programa FreeStep ® para determinar o centro de gravidade de cada individuo possibilitando a captura da oscilacao por meio da plataforma durante a manutencao da postura estatica. Para analise estatistica, utilizaram-se o software Bioestat versao 5.0 e o teste T de Stundent para comparacao de medias entre os grupos estudados. O nivel de significância fixado foi de p<0,05. Resultados : Verificou-se que a velocidade media de oscilacao em mm/s (p=0,0327) e o deslocamento L/L em mm/s (p=0,0014) na condicao olhos abertos apresentaram diferenca estatistica significante entre os grupos, bem como o deslocamento A/P em mm/s (p=0,0244) com olhos fechados. Conclusao : Ha alteracoes significativas na manutencao do equilibrio estatico em individuos estrabicos no deslocamento L/L e na velocidade media de oscilacao quando com os olhos abertos, no entanto existe uma correlacao positiva em relacao ao deslocamento A/P na condicao olhos fechados quando comparados com os individuos com visao normal.
Antiparkinson Prodrugs (2008)

Parkinson's disease (PD) is a progressive, neurodegenerative disorder which involves the loss of dopaminergic neurons of the substantia nigra pars compacta. Current therapy is essentially symptomatic, and L-Dopa (LD), the direct precursor of dopamine(DA), is the treatment of choice in more advanced stages of the disease. Substitution therapy with LD is, however, associated with a number of acute problems. The peripheral conversion of LD by amino acid decarboxylase (AADC) to DA is responsible for the typical gastrointestinal (nausea, emesis) and cardiovascular (arrhythmia, hypotension) side effects. To minimize the conversion to DA outside the central nervous system (CNS) LD is usually given in combination with peripheral inhibitors of AADC (carbidopa and benserazide). In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability and the wide range of inter- and intra-patient variations of plasma levels are the drug's physical-chemical properties: low water and lipid solubility, resulting in unfavourable partition, and the high susceptibility to chemical and enzymatic degradation. In order to improve the bioavailability, the prodrug approach appeared to be the most promising and some LD prodrugs have been prepared in an effort to solve these problems. We report here a review of progress in antiparkinson prodrugs, focusing on chemical structures mainly related to LD, DA and dopaminergic agonists.
Cellular Requirements for Cytokine Production in Response to the Immunomodulators Imiquimod and S-27609 (1995)

Imiquimod (R-837) and its analog, S-27609, belong to a class of imidazoquinolinamines that have potent antitumor and antiviral effects in animals. Much of their biologic activity is a result of the induction of cytokines, including interferon-alpha (IFN-alpha), tumor necrosis factor alpha (TNF), and others. In this study, the cells responsible for S-27609- and imiquimod-induced cytokine production were characterized. E rosette+ T cells were not the major cell population responsible for IFN-alpha and TNF in response to S-27609 or imiquimod. In contrast, E rosette- cells and unseparated PBMC produced similar concentrations of IFN-alpha and TNF in response to S-27609 and imiquimod. Elimination of monocytes by treatment with the lysosomotropic agent L-leucine methyl ester (LME) or depletion using antibody to CD14 and immunomagnetic beads abrogated IFN-alpha and TNF production induced by S-27609, imiquimod, or LPS but not poly(I)/(C). LME treatment also abolished interleukin (IL)-1 alpha, IL-beta, IL-6, and IL-8 production stimulated by S-27609 and imiquimod. Removal of HLA-DR+ or CD36+ monocytes also caused a significant reduction in S-27609- and imiquimod-induced IFN-alpha and TNF. Elimination of B cells, NK cells, and dendritic cells did not significantly reduce cytokine induction in response to S-27609. Thus, the cell population responsible for the majority of cytokine release in human PBMC in response to S-27609 and imiquimod is a E rosette-, CD14+, CD36+, HLA-DR+ monocyte.
Cognitive-Behavioral Group Therapy for Multiple-DUI Offenders (1986)

Marlatt's (1978) Cognitive-Behavioral Model of relapse and Ellis' (1977) Rational-Emotive Therapy (RET) were used as bases to develop group therapy programs for multiple DUI offenders. The common elements and specific contents of the groups are described. A program evaluation battery administered pre and post treatment found no differences among the two specific treatment programs and an unstructured therapy group on both drinking and non-drinking measures except assertiveness. The implications and alternative explanations of these results are discussed.
Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR (1995)

To further explore the controversial potential for extrahepatic replication of hepatitis C virus (HCV), the highly strand-specific rTth method of reverse transcriptase PCR was used to examine sera, liver, peripheral blood mononuclear cells, and other extrahepatic tissues from HCV-infected chimpanzees and humans. Positive-strand HCV RNA was present in the liver at approximately 10-fold-higher levels than negative-strand HCV RNA. No negative-strand RNA was detected in peripheral blood mononuclear cells or other extrahepatic tissues despite the presence of abundant positive-strand RNA. These data demonstrate that within the limits of sensitivity of this highly strand-specific reverse transcriptase PCR method, no extrahepatic replication of HCV was detected.
Chemical Modification of a Bridging Ligand Inside a Metal–Organic Framework while Maintaining the 3D Structure (2008)

Abstract A new metal–organic framework (MOF) with amino groups situated inside the pores has been synthesized. This MOF has been modified by post‐synthesis with two different functionalities. The crystal structures of the two functionalized MOFs clearly demonstrate that it is possible to transform the cavities of a MOF without modifying its original 3D structure. These unprecedented results open up tremendous possibilities in the field of MOF chemistry because many potential applications in the fields of catalysis, material science ornanochemistry can be envisaged when applying the reported synthetic pathway.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
Hidden Memories: Frontline Memory T Cells and Early Pathogen Interception (2012)

Immunologic memory reflects the ability of a host to more effectively respond to a re-encounter with a particular pathogen than the first encounter, and when a vaccine mimics the first encounter, comprises the basis of vaccine efficacy. For T cells, memory is often equated with the anamnestic response, the ability of secondary lymphoid tissue-based (central) memory T cells to respond to pathogen exposure with a more rapid and higher magnitude production and infection-site delivery of pathogen-specific effector cells than observed in naive hosts. However, increasing evidence supports a fundamentally different kind of T cell memory in which differentiated, long-lived effector memory T cells, prepositioned in sites of potential pathogen invasion or rapidly mobilized to such sites from blood and marginated pools, intercept and potentially control/eliminate pathogen within hours of infection. In this article, we review the evidence for this "hidden" T cell memory and its implication for vaccine development.
Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21) (2003)

The transmembrane proto-oncogene receptor tyrosine kinase (RTK) ROS is an orphan receptor that is aberrantly expressed in neoplasms of the central nervous system. Here, we report the fusion of its carboxy-terminal kinase domain to the amino-terminal portion of a protein called FIG (Fused in Glioblastoma) in a human glioblastoma multiforme (GBM). By characterizing both FIG and ROS genes in normal and in U118MG GBM cells, we determined that an intra-chromosomal homozygous deletion of 240 kilobases on 6q21 is responsible for the formation of the FIG-ROS locus. The FIG-ROS transcript is encoded by 7 FIG exons and 9 ROS-derived exons. We also demonstrate that the FIG-ROS locus encodes for an in-frame fusion protein with a constitutively active kinase activity, suggesting that FIG-ROS may act as an oncogene. This is the first example of a fusion RTK protein that results from an intra-chromosomal deletion, and it represents the first fusion RTK protein isolated from a human astrocytoma.
A Study to Determine the Effects of Food and Multiple Dosing on the Pharmacokinetics of Vorinostat Given Orally to Patients with Advanced Cancer (2006)

Vorinostat concentrations were qualitatively similar after single and multiple doses. A high-fat meal increased the extent and modestly decreased the rate of absorption of vorinostat; this effect is not anticipated to be clinically meaningful. Continued investigation of 400 mg vorinostat given once daily in phase II and III efficacy studies is warranted.
Focal Delivery of AAV2/1-transgenes Into the Rat Brain by Localized Ultrasound-induced BBB Opening (2013)

Delivery of drugs and macromolecules to the central nervous system (CNS) is hindered by the blood-brain barrier (BBB). Several approaches have been used to overcome this hindrance to facilitate the treatment of various CNS diseases. We now present results showing that chimeric adeno-associated virus 2/1 (AAV2/1) particles containing the coding region for the LacZ gene are efficiently delivered into the rat brain upon intravenous (IV) administration after BBB opening by focused ultrasound in the presence of vascular acoustic resonators. We show that the transgene is correctly and efficiently expressed in cells located in the neighborhood of the insonated focus, especially in the vicinity of small vessels and capillaries. Histochemical LacZ staining allows the identification of large amounts of cells expressing the enzymatically active protein. Using double immunofluorescence (IF) with antibodies against tubulinIII and bacterial LacZ, we identified these cells to be mostly neurons. A small proportion of the transduced cells was recognized as glial cells, reacting positive in the IF with antibodies against astrocytic markers. These results demonstrate that our approach allows a very specific, localized, and efficient expression of intravenously administered transgenes in the brain of rats upon ultrasound-induced BBB opening.Molecular Therapy - Nucleic Acids (2013) 2, e73; doi:10.1038/mtna.2012.64; published online 19 February 2013.
Optimal realization of arbitrary forces in a magnetic stereotaxis system (1996)

Very small implanted permanent magnets guided by large electromagnetic coils have been proposed previously as a method for delivering hyperthermia to or guiding catheters through brain tissue. This procedure is termed "magnetic stereotaxis". Early efforts employed a single coil on a movable boom, a design that proved logistically difficult to use on human patients. The present work deals instead with a design where several stationary coils are employed to develop a force on the implanted magnet. The coil current-to-force relationship is developed for this type of machine, and several optimal solutions for realizing an arbitrary static force are presented for various constraints on the orientation of the implanted permanent magnet. Costs of the different solutions are compared in several examples using a mathematical model based on the Magnetic Stereotaxis System (MSS) developed by Stereotaxis, Inc., the University of Virginia, and Wang NMR.
Changes with aging in the levels of amino acids in rat CNS structural elements: IV. Methionine and basic amino acids (1990)

This paper reports the distribution of methionine, histidine, lysine, arginine, and ornithine in 53 discrete brain areas of 3- and 29-month-old male Fischer 344 rats microdissected by the punch technique. Like that of the other amino acids were reported in previous papers of this series, the distribution of methionine and the basic amino acids was regionally highly heterogeneous. The ratios of levels in the areas of highest concentrations to levels in the areas of lowest concentration varied from 10 to 15 for these amino acids, except that it was 23 for arginine. This heterogeneity is also illustrated by the finding that in some areas arginine was more than 5% of the total amino acid content and in others was less than 0.5%. The distribution of methionine differed from that of the basic amino acids, which were high in hypothalamic areas and low in the limbic system. With aging, methionine and basic amino acids, like the other amino acids studied in this series, mainly decreased in level, although in a few cases increases could be seen. Significant decreases were noted more than five times as often as increases.
Coexistence of Anti-Phospholipid Antibodies and Endothelial Perturbation in Systemic Lupus Erythematosus Patients With Ongoing Prothrombotic State (1997)

This study shows that in SLE patients, aPL positivity is associated with an ongoing prothrombotic state only in the presence of endothelial perturbation. Our findings also suggest that aPLs and TNF-alpha might cooperate in inducing endothelial perturbation.
Hybrid Approach to Faster Functional Verification with Full Visibility (2007)

For functional verification, software simulation provides full controllability and observability, whereas hardware emulation offers speed. This article describes a new platform that leverages the advantages of both. This platform implements an efficient scheme to record the internal behavior of an FPGA emulator and replay the relevant segment of a simulation in a software environment for debugging. Experimental results show an order-of-magnitude savings in debugging time compared to a software-only simulation approach.