gebhart/patrepeval huggingface dataset:
Tau prions from Alzheimer’s disease and chronic traumatic encephalopathy patients propagate in cultured cells (2016)

Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from AGD, CBD, and PSP patient samples, which contain four-repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R isoforms, were unable to robustly infect either 3R- or 4R-expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.
Preparation and Characterization of Methylene blue Nanoparticles for Alzheimer’s Disease and Other Tauopathies (2013)

Methylene blue (MB) has been shown to slow down the progression of the Alzheimer's disease (AD) and other tauopathies; however distribution of MB into the brain is limited due its high hydrophilicity. In this study, we aimed to prepare novel hydrophobic glutathione coated PLGA nanoparticles to improve bioavailability of MB in the brain. Glutathione coated poly-(lactide-co-glycolide) (PLGA-b-PEG) nanoparticles (NPs) were prepared and tested in two different cell culture models of AD expressing microtubule associated protein tau (tau). The NPs showed a particle size averaging 136.5±4.4nm, which is suitable for the blood brain barrier (BBB) permeation. The in vitro release profile of the NPs exhibited no initial burst release and showed sustained drug release for up to 144 hours. Interestingly, treatment of newly formulated MB-NPs showed a potent reduction in both endogenous and over expressed tau protein levels in human neuroblastoma SHSY-5Y cells expressing endogenous tau and transfected HeLa cells over-expressing tau protein, respectively. Furthermore, in vitro BBB Transwell™ study showed significantly higher permeation of MB-NP compared to the MB solution through the co culture of rat brain endothelial 4 (RBE4) and C6 astrocytoma cells (p<0.05). The proposed MB loaded nanoparticles could provide a more effective treatment option for AD and many other related disorders.
Glycosylation of Pseudomonas aeruginosa Strain Pa5196 Type IV Pilins with Mycobacterium-Like α-1,5-Linked d -Ara f Oligosaccharides (2006)

Pseudomonas aeruginosa is a gram-negative bacterium that uses polar type IV pili for adherence to various materials and for rapid colonization of surfaces via twitching motility. Within the P. aeruginosa species, five distinct alleles encoding variants of the structural subunit PilA varying in amino acid sequence, length, and presence of posttranslational modifications have been identified. In this work, a combination of mass spectrometry and nuclear magnetic resonance spectroscopy was used to identify a novel glycan modification on the pilins of the group IV strain Pa5196. Group IV pilins continued to be modified in a lipopolysaccharide (wbpM) mutant of Pa5196, showing that, unlike group I strains, the pilins of group IV are not modified with the O-antigen unit of the background strain. Instead, the pilin glycan was determined to be an unusual homo-oligomer of alpha-1,5-linked d-arabinofuranose (d-Araf). This sugar is uncommon in prokaryotes, occurring mainly in the cell wall arabinogalactan and lipoarabinomannan (LAM) polymers of mycobacteria, including Mycobacterium tuberculosis and Mycobacterium leprae. Antibodies raised against M. tuberculosis LAM specifically identified the glycosylated pilins from Pa5196, confirming that the glycan is antigenically, as well as chemically, identical to those of Mycobacterium. P. aeruginosa Pa5196, a rapidly growing strain of low virulence that expresses large amounts of glycosylated type IV pilins on its surface, represents a genetically tractable model system for elucidation of alternate pathways for biosynthesis of d-Araf and its polymerization into mycobacterium-like alpha-1,5-linked oligosaccharides.
The imbalance between Bim and Mcl‐1 expression controls the survival of human myeloma cells (2004)

Multiple myeloma is a fatal B cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that appears to regulate cell survival through the JAK/STAT pathway. In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1. The three major Bim isoforms are expressed in myeloma cells and are negatively regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly associated with Mcl-1 in viable myeloma cells while this interaction is disrupted under apoptosis induction. Of note, while Bim is also found strongly associated to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows Bim to exercise its pro-apoptotic function and to activate Bax.
Transcription Factors E2A, FOXO1 and FOXP1 Regulate Recombination Activating Gene Expression in Cancer Cells (2011)

It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only. Recently Igs have been found to be expressed in various human cancer cells and promote tumor growth. Recombination activating gene 1 (RAG1) and RAG2, which are essential enzymes for initiating variable-diversity-joining segment recombination, have also been found to be expressed in cancer cells. However, the mechanism of RAG activation in these cancer cells has not been elucidated. Here, we investigated the regulatory mechanism of RAG expression in four human cancer cell lines by analyzing transcription factors that induce RAG activation in B cells. By RT-PCR, Western blot and immunofluorescence, we found that transcription factors E2A, FOXO1 and FOXP1 were expressed and localized to the nuclei of these cancer cells. Over-expression of E2A, FOXO1 or Foxp1 increased RAG expression, while RNA interference of E2A, FOXO1 or FOXP1 decreased RAG expression in the cancer cells. Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo. These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.
Ex vivo analysis of cytotoxic T lymphocytes to measles antigens during infection and after vaccination in Gambian children. (1998)

The study of cytotoxic T cell responses to measles antigens during infection and after vaccination may provide insight into the immunopathology of the infection. It will also provide a knowledge of the immunity conferred by wild or attenuated virus, which will help in the design of new vaccines. Direct cytotoxic T cell responses, which did not require in vitro restimulation, were measured from peripheral blood by a standard 51Cr-release assay in 35 patients with acute measles, using HLA class I matched allogeneic B cells as targets. 77% showed specific responses to measles fusion protein, 69% to the hemagglutinin, and 50% to the nucleoprotein. These responses, which were related to severity of disease and history of previous vaccination, had waned by 14-24 wk after measles when memory responses to the same antigens could be elicited by restimulation in 71% of the 13 patients tested. A similar pattern followed vaccination: direct cytotoxic responses to fusion and hemagglutinin proteins were shown in 70% of the 20 children tested while 50% responded to the nucleoprotein. These responses, which were mediated by both CD8(+) and CD4(+) cells, faded over 6 wk when memory responses could be restimulated. Thus, a vigorous cytotoxic T lymphocyte response to fusion, hemagglutinin, and nucleoproteins is important in both natural and vaccine-induced immunity to measles.
Structural Basis for Importin-α Binding of the Human Immunodeficiency Virus Tat (2017)

HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning <sup>48</sup>GRKKRR, and a cell penetrating peptide (CPP) signal spanning <sup>48</sup>GRKKRRQRRRAPQN. However, the mechanism by which this NLS/CPP region mediates interaction with the nuclear import receptors remains to be resolved structurally. Here, we establish that the HIV-1 Tat:NLS/CPP is able to form a stable and direct interaction with the classical nuclear import receptor importin-α and using x-ray crystallography, we have determined the molecular interface and binding determinants to a resolution of 2.0 Å. We show for the first time that the interface is the same as host factors such as Ku70 and Ku80, rather than other virus proteins such as Ebola VP24 that bind on the outer surface of importin-α.
Collection of Capillary Electrophoresis Fractions on a Moving Membrane (2003)

During the last 10 years, capillary electrophoresis (CE) has developed into a powerful analytical method for a wide variety of applications. It tends to replace traditional slab-gel electrophoresis for the separation of complex biological samples (DNA, proteins, carbohydrates) (1). The ability to further analyze the separated components using specific secondary reactions, analogous to well-established methods such as the Southern blot (2) and direct blotting (3) is important for the full development of this rapidly growing method. The total amount of sample separated in CE is very small when compared to slab gels, but thanks to the sensitivity and miniaturization of modern detection methods, it may still be sufficient for many postseparation analysis applications, such as hybridization, sequencing, enzyme digestion, reamplification by polymerase chain reaction (PCR), and so on.
Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade (2016)

As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy-induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens.
Analgesic effect of agmatine and its enhancement on morphine analgesia in mice and rats. (1999)

Agmatine has weak analgesic effects and potentiates morphine and clonidine analgesia by activation of imidazoline receptors.
INSTRUMENTAL TEXTURE PROFILE ANALYSIS WITH PARTICULAR REFERENCE TO GELLED SYSTEMS (1996)

ABSTRACT Instrumental Texture Profile Analysis (TPA) was developed about 30 years ago, constituting an interesting way of analyzing a series of textural parameters in only one test. Since then much work has been done and new tools have been developed. This paper focuses on gelled food systems, reviewing and discussing the evolution of the initial terminology, testing conditions and sampling methods. New parameters, experimental and calculation methods, and some newly proposed are also analyzed, updating the instrumental TPA as applied to gelled systems.
Structural Features of Oxide Coatings on Aluminum (1953)

The structural features of the porous type of anodic oxide coating applied to aluminum have been investigated with the electron microscope. These coatings consist of close‐packed cells of oxide, predominately hexagonal in shape, each of which contains a single pore. Pore size is a function of the electrolyte used and is independent of forming voltage. Wall thickness and barrier thickness are primarily a function of forming voltage and are affected to a minor degree by the electrolyte type. Pertinent dimensions of anodic coatings formed in sulfuric acid, oxalic acid, chromic acid, and phosphoric acid electrolytes are presented, and formulas are given for calculating the cell size and pore volume of these coatings.
Cloning and chromosomal assignment of a widely expressed human receptor‐like protein‐tyrosine phosphatase (1990)

Insight into the regulation of the actions of the protein-tyrosine kinases will be greatly facilitated by the full characterization of the family of protein-tyrosine phosphatases. A search for novel phosphatases resulted in the isolation of a cDNA, termed HLPR, encoding a member of the family of human receptor-like protein-tyrosine phosphatases: its cDNA sequence predicts a protein of 793 amino acids (unglycosylated Mr 87,500) and includes a 121 residue extracellular domain, a single transmembrane segment, and and two tandem intra-cytoplasmic catalytic domains. The HLPR genes is located on human chromosome 20, and the protein it encodes likely plays a fundamental role in the physiology of all cells as its expression appears to be ubiquitous.
Neural Control of Tongue Movement With Respect To Respiration and Swallowing (2001)

The tongue must move with remarkable speed and precision between multiple orofacial motor behaviors that are executed virtually simultaneously. Our present understanding of these highly integrated relationships has been limited by their complexity. Recent research indicates that the tongue s contribution to complex orofacial movements is much greater than previously thought. The purpose of this paper is to review the neural control of tongue movement and relate it to complex orofacial behaviors. Particular attention will be given to the interaction of tongue movement with respiration and swallowing, because the morbidity and mortality associated with these relationships make this a primary focus of many current investigations. This review will begin with a discussion of peripheral tongue muscle and nerve physiology that will include new data on tongue contractile properties. Other relevant peripheral oral cavity and oropharyngeal neurophysiology will also be discussed. Much of the review will focus on brainstem control of tongue movement and modulation by neurons that control swallowing and respiration, because it is in the brainstem that orofacial motor behaviors sort themselves out from their common peripheral structures. There is abundant evidence indicating that the neural control of protrusive tongue movement by motoneurons in the ventral hypoglossal nucleus is modulated by respiratory neurons that control inspiratory drive. Yet, little is known of hypoglossal motoneuron modulation by neurons controlling swallowing or other complex movements. There is evidence, however, suggesting that functional segregation of respiration and swallowing within the brainstem is reflected in somatotopy within the hypoglossal nucleus. Also, subtle changes in the neural control of tongue movement may signal the transition between respiration and swallowing. The final section of this review will focus on the cortical integration of tongue movement with complex orofacial movements. This section will conclude with a discussion of the functional and clinical significance of cortical control with respect to recent advances in our understanding of the peripheral and brainstem physiology of tongue movement.
Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds both VEGFR-1 and VEGFR-2 (2007)

Bovine papular stomatitis virus (BPSV), a member of the genus Parapoxvirus, causes proliferative dermatitis in cattle and humans. Other species of the genus cause similar lesions, the nature of which has been attributed, at least in part, to a viral-encoded vascular endothelial growth factor (VEGF) that induces vascularization and dermal oedema through VEGF receptor-2 (VEGFR-2). The results of this study showed that BPSV strain V660 encodes a novel VEGF and that the predicted BPSV protein showed only 33-52% amino acid identity to VEGFs encoded by the other species of the genus. BPSV VEGF showed higher identity to mammalian VEGF-A (51%) than the other parapoxviral VEGFs (31-46%). Assays of the purified BPSV VEGF (BPSVV660VEGF) demonstrated that it was also functionally more similar to VEGF-A, as it showed significant binding to VEGFR-1 and induced monocyte migration. Like VEGF-A and the other viral VEGFs, BPSVV660VEGF bound VEGFR-2 with high affinity. Sequence analysis and structural modelling of BPSVV660VEGF revealed specific residues, outside the known receptor-binding face, that are predicted either to influence VEGF structure or to mediate binding directly to the VEGFRs. These results indicate that BPSVV660VEGF is a biologically active member of the VEGF family and that, via its interaction with VEGFR-2, it is likely to contribute to the proliferative and highly vascularized nature of BPSV lesions. This is also the first example of a viral VEGF acting via VEGFR-1 and influencing haematopoietic cell function. These data suggest that BPSVV660VEGF is an evolutionary and functional intermediate between VEGF-A and the other parapoxviral VEGFs.
Femtosecond Dynamics of Unimolecular and Unrestricted Bimolecular Reactions (1998)

The results of two time-resolved experiments using femtosecond laser pulses are presented. In the first, molecular photoinduced detachment of I2 from methylene iodide is studied. The progress of the reaction is monitored by selective detection of fluorescence from the iodine product; molecular dynamics are probed by depletion of the fluorescent state. Pump−probe spectroscopy of the halogen moiety following high-energy (12 eV) excitation reveals that the reaction proceeds by a concerted asynchronous mechanism. The second experiment is a real-time study of an unrestricted bimolecular reaction. In this process, gas phase mercury atoms are photoassociated to an electronically excited state using a femtosecond pulse; the real-time dynamics of the resulting excimers are probed by fluorescence depletion using a second pulse. Analysis of the rotational anisotropy in the nascent dimers reveals the degree of rotational excitation in the excited state and indicates the impact parameter selectivity of the photoassociation process.
Selective decrease in colonic CD56+ T and CD161+ T cells in the inflamed mucosa of patients with ulcerative colitis (2007)

Selective reduction in the population of colonic mucosal NKR(+) T cells may contribute to the development of intestinal inflammation in UC.
New supramolecular arrays based on interactions between carboxylate and urea groups: solid-state and solution behavior (1998)

The urea–carboxylate interaction is introduced as a potentially general motif for the control of solid-state packing patterns. We show that simple phenylurea carboxylate derivatives can form extended hydrogen-bonded ribbons in the crystal in which the zig-zag shape of the aggregate is controlled by the relative orientation of the two substituents about the phenyl core. We also show that an alternative type of aggregation may occur in solution involving the formation of cyclic aggregates. Again, the size and stability of the aggregate is dependent on the substitution pattern of the monomer.
Autism spectrum disorders: a review of measures for clinical, health services and cost–effectiveness applications (2012)

Autism spectrum disorders (ASDs) are characterized by impairments in social interaction, communication and behavioral functioning that can affect the health-related quality-of-life outcomes of the affected child and the family. ASDs have increased in prevalence, leading to a demand for improved understanding of the comparative effectiveness of different pharmacologic, behavioral, medical and alternative treatments for children as well as systems for providing services. This review describes outcome instruments that can be used for clinical, health services and cost-effectiveness applications. There is a pressing need to identify the most appropriate instruments for measuring health-related quality-of-life outcomes in this population. Studies evaluating the cost-effectiveness of interventions or treatments for children with ASDs using the cost per quality-adjusted life year metric are lacking. Researchers have the potential to contribute greatly to the field of autism by quantifying outcomes that can inform optimal treatment strategies.
Production of Acrylic Acid through Nickel-Mediated Coupling of Ethylene and Carbon Dioxide—A DFT Study (2007)

The production of acrylic acid (CH2═CHCO2H) via homogeneous nickel-mediated coupling of ethylene (CH2═CH2) and carbon dioxide (CO2) is industrially unattractive at present due to its stoichiometric, rather than catalytic, reaction profile. We utilize density functional theory (DFT) to describe the potential energy surface for both the nickel-mediated coupling reaction and an intramolecular deactivation reaction reported to hinder the desired catalytic activity. The calculated route for the catalytic production of acrylic acid can be divided into three main parts, none of which contain significantly large barriers that would be expected to prohibit the overall catalytic process. Investigation of the catalyst deactivation reaction reveals that the proposed product lies +102.6 kJ mol−1 above the reactants, thereby ruling out this type of pathway as the cause of the noncatalytic activity. Instead, it is far more conceivable that the overall reaction thermodynamics are responsible for the lack of catalytic activity observed, with the solvation -corrected Gibbs free energy of the coupling reaction in question (i.e., CH2═CH2 + CO2 → CH2═CHCO2H) calculated to be an unfavorable +42.7 kJ mol−1.