gebhart/patrepeval huggingface dataset:
Novel regulatory functions for Toll‐like receptor‐activated B cells during intracellular bacterial infection (2011)

Infections by intracellular bacterial pathogens remain a major cause of human diseases worldwide. Despite intensive efforts, the development of effective vaccines or immunotherapies against these diseases has largely remained unsuccessful, asking for the exploration of new aspects of the host response to these pathogens. Genetic studies have demonstrated beyond doubt that cell-mediated mechanisms of host defense involving innate immunity and T cells are of crucial importance for the control of these diseases. By contrast, the role of B cells during intracellular bacterial infection has so far received little attention besides their role as antibody-producing cells. However, the general knowledge of B-cell immunology and in particular of their antibody-independent functions has greatly increased during the last years. Recently, it was found in a model of Salmonella typhimurium infection that Toll-like receptor triggering on B cells resulted through interleukin-10 secretion in a marked suppression of innate defense mechanisms ultimately leading to uncontrolled growth of the bacteria and earlier death from the disease during both primary and secondary infections. This article reviews the protective and deleterious roles of B cells during intracellular bacterial infections and discusses how manipulating their antibody-independent functions may be a powerful means to therapeutically improve host resistance against these diseases.
CD40-CD40 ligand interactions are critical in T-B cooperation but not for other anti-viral CD4+ T cell functions. (1996)

CD40-CD40 ligand (CD40L) interaction is required for the generation of antibody responses to T-dependent antigens as well as for the development of germinal centers and memory B cells. The role of the CD40-CD40L interaction in the induction of antigen-specific. Th cells and in mediating Th cell effector functions other than cognate help for B cells is less well understood. Using CD40- and CD40L-deficient mice together with lymphocytic choriomeningitis virus and vesicular stomatitis virus as viral model antigens, this study corroborates earlier findings that no lg isotype switching of virus-specific antibodies was measurable upon infection of CD40- or CD40L-deficient mice. In contrast, in vivo induction of virus-specific CD4+ T cells measured by proliferation and cytokine secretion of primed virus-specific Th cells in vitro was not crucially dependent on the CD40-CD40L interaction. In addition, virus-specific Th cells primed in a CD40-deficient environment, adoptively transferred into CD40-competent recipients, were able to mediate lg isotype switch. Th-mediated effector functions distinct from and in addition to T-B collaboration were analyzed in CD40- and CD40L-deficient and normal mice: (a) local inflammatory reactions upon LCMV infection mediated by LCMV-specific Th cells were not dependent on a functional CD40-CD40L interaction, (b) cytokine-mediated protection by CD4+ T cells primed by vesicular stomatitis virus against a challenge infection with recombinant vaccinia virus expressing the glycoprotein of vesicular stomatitis virus was found to be equivalent in CD40L-deficient and normal mice. Thus, CD40-CD40L interaction plays a crucial role in T-B interactions for Th-dependent activation of B cells but not, or to a much lesser extent, in T cell activation, antigen-specific Th cell responses in vitro, and for interleukin-mediated Th cell effector functions in vivo.
Specific N-linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies (1997)

During progression to AIDS in simian immunodeficiency virus (SIV) Mne-infected macaques, viral variants are selected that encode sequences with serine and threonine changes in variable region 1 (V1) of the surface component of the viral envelope protein (Env-SU). Because these serine and threonine amino acid changes are characteristic of sites for O-linked and N-linked glycosylation, we examined whether they were targets for modification by carbohydrates. For this purpose, we used several biochemical methods for analyzing the Env-SU protein encoded by chimeras of SIVMneCL8 and envelope sequences cloned from an SIVMneCL8-infected Macaca nemestrina during clinical latency and just after the onset of AIDS. The addition of an N-linked glycan was demonstrated by changes in the electrophoretic mobility of Env-SU, and this was verified by specific glycanase digestions and a detailed analysis of the molecular mass of partially purified Env-SU by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Molecular mass calculations by MALDI-TOF MS also demonstrated an increased mass, from 102.3 to 103.5 kDa, associated with serine and threonine residues predicted to be O-linked glycosylation sites. Together, these data provide the first direct evidence that the carbohydrate profile of Env-SU is distinct in SIV variants that evolve during infection of the host. Moreover, our studies show that these changes in glycosylation in V1 were directly associated with changes in antigenicity. Specifically, serine and threonine changes in V1 allowed the virus to escape neutralization by macaque sera that contained antibodies that could neutralize the parental virus, SIVMneCL8. The escape from antibody recognition appeared to be influenced by either O-linked or N-linked carbohydrate additions in V1. Moreover, when glycine residues were engineered at the positions where serine and threonine changes evolve in V1 of SIVMneCL8, there was no change in antigenicity compared to SIVMneCL8. This suggests that the amino acids in V1 are not part of the linear epitope recognized by neutralizing antibody. More likely, V1-associated carbohydrates mask the major neutralizing epitope of SIV. These experiments indicate that the selection of novel glycosylation sites in the V1 region of envelope during the course of disease is driven by humoral immune responses.
Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120 (2012)

A large number of anti-HIV-1 antibodies targeting the CD4-binding site (CD4bs) on the envelope glycoprotein gp120 have recently been reported. These antibodies, typified by VRC01, are remarkable for both their breadth and their potency. Crystal structures have revealed a common mode of binding for several of these antibodies; however, the precise relationship among CD4bs antibodies remains to be defined. Here we analyze existing structural and sequence data, propose a set of signature features for potent VRC01-like (PVL) antibodies, and verify the importance of these features by mutagenesis. The signature features explain why PVL antibodies derive from a single germ-line human V(H) gene segment and why certain gp120 sequences are associated with antibody resistance. Our results bear on vaccine development and structure-based design to improve the potency and breadth of anti-CD4bs antibodies.
Time-lock Puzzles and Timed-release Crypto (1996)

1 Introduction Our motivation is the notion of &amp;amp;quot;timed-release crypto, &amp;amp;quot; where the goal is to encrypt a message so that it can not be decrypted by anyone, not even the sender, until a pre-determined amount of time has passed. The goal is to &amp;amp;quot;send information into the future. &amp;amp;quot; This problem was first discussed by Timothy May [6]. What are the applications of &amp;amp;quot;timed-release crypto&amp;amp;quot;? Here are a few possibilities (some due to May):
Area-Selective Atomic Layer Deposition Using Self-Assembled Monolayer and Scanning Probe Lithography (2009)

We investigated area-selective atomic layer deposition (ALD) of zirconia using a self-assembled monolayer (SAM) and atomic force microscopy (AFM) oxidation lithography as a method of fabricating nanostructures. A SAM layer was used as a chemical mask for the ALD process, and AFM oxidation lithography was used as a nanoscale patterning tool. AFM oxidation lithography was applied to create oxide patterns on octadecyltrichlorosilane SAM-grown silicon substrates. Subsequent HF etching removed the oxide patterns locally, exposing a silicon substrate underneath. After 100 cycles of the ALD process, ALD nanostructures high and sub-100 nm wide were fabricated with no detectable Zr element outside the pattern defined by AFM oxidation lithography. The present method makes it possible to construct advanced metal-oxide-semiconductor field effect transistor and quantum confinement structures with a wide range of ALD precursor materials.
Creation of Hybrid Nanorods From Sequences of Natural Trimeric Fibrous Proteins Using the Fibritin Trimerization Motif (2008)

Stable, artificial fibrous proteins that can be functionalized open new avenues in fields such as bionanomaterials design and fiber engineering. An important source of inspiration for the creation of such proteins are natural fibrous proteins such as collagen, elastin, insect silks, and fibers from phages and viruses. The fibrous parts of this last class of proteins usually adopt trimeric, beta-stranded structural folds and are appended to globular, receptor-binding domains. It has been recently shown that the globular domains are essential for correct folding and trimerization and can be successfully substituted by a very small (27-amino acid) trimerization motif from phage T4 fibritin. The hybrid proteins are correctly folded nanorods that can withstand extreme conditions. When the fibrous part derives from the adenovirus fiber shaft, different tissue-targeting specificities can be engineered into the hybrid proteins, which therefore can be used as gene therapy vectors. The integration of such stable nanorods in devices is also a big challenge in the field of biomechanical design. The fibritin foldon domain is a versatile trimerization motif and can be combined with a variety of fibrous motifs, such as coiled-coil, collagenous, and triple beta-stranded motifs, provided the appropriate linkers are used. The combination of different motifs within the same fibrous molecule to create stable rods with multiple functions can even be envisioned. We provide a comprehensive overview of the experimental procedures used for designing, creating, and characterizing hybrid fibrous nanorods using the fibritin trimerization motif.
Motor fluctuations in Parkinson's disease: pathophysiology and treatment (1999)

At the initial stages of Parkinson's disease (PD), levodopa (LD) is able to reduce most motor symptoms and to significantly improve the patient's quality of life. However, in the vast majority of patients with prolonged LD usage, some decline in efficacy occurs and motor complications eventually begin to appear. These complications consist not only of daily fluctuations in the voluntary motor performance often accompanied by involuntary movements, but also of fluctuations in cognitive, autonomic, and sensory functions. Several recent studies on LD complications in PD have led to a better understanding of their pathophysiology and of the possible therapeutic interventions, and a summary of these findings is presented in this review. Different observations now suggest that postsynaptic pharmacodynamic factors play a major role in determining fluctuations in PD. Two explanations are given: chronic intermittent dopaminergic therapy may lead to postsynaptic receptor downregulation in PD; or, receptor changes in the striatum may occur independently of treatment as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of the nigrostriatal pathway. The hypothesis of reversible postsynaptic changes as the main mechanism underlying a fluctuating response to LD lends itself to a possible pharmacological manipulation of the dopaminergic response to reverse, or even avoid, motor fluctuations (initial monotherapy with dopamine agonists and early combination LD/dopamine agonists). The role of peripheral pharmacokinetics factors is also critical and the use of controlled release LD formulations, of monoamine oxidase (MAO)-B and of catechol-O-methyltransferase (COMT) inhibitors may all, to a different degree, improve such phenomena. In the last decade, there has been a resurgence in surgical therapies in advanced PD, due to higher levels of accuracy and safety provided by the new surgical devices, and to a more precise localization of the target areas allowed by the neurophysiological mapping techniques. The surgical procedures currently used in advanced PD are stereotactic brain lesions (internal globus pallidus and subthalamic nucleus), chronic brain stimulation (of the same nuclei) and striatal grafting of dopamine-producing cells. All these procedures have already shown their efficacy in the management of severe fluctuations in PD, but their indications, and relative advantages and disadvantages, are still the subject of considerable debate and controversy.
Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. (1993)

We have investigated the effect of chemotherapeutic and DNA damaging agents on binding of the tumor suppressor phosphoprotein p53 to its consensus DNA sequence. Activation of p53-DNA binding was seen for treatment with radiation, hydrogen peroxide, actinomycin D, Adriamycin, etoposide, camptothecin, 5-fluorouracil, mitomycin C, and cisplatin. These results showed that DNA strand breaks were sufficient to lead to increased levels of p53. The protein synthesis inhibitor cycloheximide blocks the increase in p53 following DNA damage. The increase in p53 activation in camptothecin treated cells may result, at least in part, from an increased half-life of the protein and consequent increases in intracellular protein concentration.
Synthesis of 14C labelled electrophilic ligands of the colchicine binding site of tubulin: Chloroacetates of demethylthiocolchicines and of N‐acetylcolchinol; isothiocyanate of 9‐deoxy‐N‐acetylcolchinol (1993)

Abstract 14 C‐Chloroacetates of 2‐demethylthiocolchicine 7 (specific activity 55.0 mCi/mmol, radiochemical yield 26.1%), and of 3‐demethylthiocolchicine 8 (specific activity 55.0 mCi/mmol, radiochemical yield 5.7%) were synthesized and found to covalently bind with high specificity to the β‐subunit of tubulin. The 14 C‐chloroacetate of N ‐acetylcolchinol 5 (specific activity 56.0 mCi/mmol, radiochemical yield 7.8%) and the 14 C‐isothiocyanate 6 (specific activity 50.0 mCi/mmol, radiochemical yield 32%) were also prepared and found to react covalently with tubulin but in a nonspecific manner. With the radiolabelled chloroacetates 7 and 8 two compounds are now available to further characterize the colchicine binding site on the β subunit of tubulin.
TRPV1 Receptor: A Target Treatment of Pain, Cough, Airway Disease and Urinary Incontinence (2005)

The TRPV1 channel is mainly expressed in sensory nerves. Activation of the channel induces neuropeptide release from central and peripheral sensory nerve terminals, resulting in the sensation of pain, neurogenic inflammation, smooth muscle contraction and cough. The TRPV1 channel can be activated by vanilloids such as capsaicin, as well as endogenous stimulators including H(+), heat, lipoxygenase products and anandamide. TRPV1 channel function is upregulated by several endogenous mediators present in inflammatory conditions, which decreases the threshold for activation of the channel. Under these conditions, TRPV1 can be activated by physiological body temperature, slight acidification or lower concentration of TRPV1 agonists. There is evidence that TRPV1 plays a role in the development of pathophysiological changes and symptoms in several diseases. In this review, we discuss TRPV1 channel activation and regulation in normal and diseased conditions, the role of TRPV1 in pain, cough, asthma and urinary incontinence, and the potential use of TRPV1 antagonists as a novel therapy for these diseases.
Characterization of human interferon-gamma and human interleukin-2 from recombinant mammalian cell lines and peripheral blood lymphocytes. (1991)

Human interleukin-2 (IL-2) and human interferon-gamma (IF-gamma) isolated from transfected heterologous cell lines were structurally compared with their natural counterparts isolated from peripheral blood lymphocytes (PBL). Several forms of IL-2 and IFN-gamma that were primarily due to differential glycosylation were produced by all cell types studied. Comparable molecular weights and sugar compositions were found for variants of natural and mammalian-derived recombinant IL-2, and variants of natural and mammalian-derived recombinant IFN-gamma. Furthermore, the specific biological activities of the natural and mammalian-derived recombinant lymphokines were similar and comparable to the specific activity of the Escherichia coli-derived recombinant proteins.
Direct Synthesis of Nanoceria in Aqueous Polyhydroxyl Solutions (2007)

Nanoceria has shown excellent biomedical properties for potential use in treatment of diseases caused by reactive oxygen species (ROS). In the present work, the synthesis and redox chemistry of nanoceria in the presence of polyhydroxyl groups such as glucose and dextran are reported. The effect of both acidic and basic medium on the synthesis and oxidation state stability of nanoceria in the absence of buffer was examined using UV−vis spectroscopy and transmission electron microscopy. The basic and acidic mediums show a difference in the synthesis of nanoceria in terms of the size and structure without interfering with the redox chemistry. A comparison of pure and aqueous saccharides suspension of nanoceria in acid/base media undergoing redox transformation is also reported in this paper.
A One Gigasample per Second Transient Recorder (1979)

A DC-to-200MHz, CCD-based transient data recorder is currently under development. Multiple recorders will be operated via a conventional computer interface. Each recorder is designed to acquire 512 samples of data at intervals as small as one nanosecond (±25ps) and to an amplitude accuracy of eight bits (±0.2%). Developmental data is presented.
Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase. (1993)

Autoantibodies to five aminoacyl-tRNA synthetases have been reported, and all have been associated with a syndrome of myo- sitis and interstitial lung disease. Four of these synthetases exist free in the cytoplasm, but the fifth, isoleucyl-tRNA syn- thetase (recognized by anti-OJ autoantibodies), is a compo- nent of the multi-enzyme complex containing at least seven synthetases. In an effort to better understand the origins of these antibodies, we examined sera from 11 patients with anti- OJ autoantibodies for evidence of reaction with other components of the complex. All sera showed a characteristic pattern of 10 protein bands by immunoprecipitation from HeLa cell extract. 10 of 11 sera significantly inhibited isoleucyl-tRNA synthetase enzyme activity. Serum and IgG from four patients also inhibited leucyl-tRNA synthetase activity, and serum and IgG from two inhibited lysyl-tRNA synthetase. Immunoblotting experiments supported reaction of the two sera with lysyl- tRNA synthetase, and revealed additional reactivity of three sera with a 160-kD component believed to be glutaminyl-tRNA synthetase. Despite reaction of some sera with additional syn- thetases, the immunoprecipitated tRNA appeared the same with all sera, and functioned as tRNAi'e.
Microwave assisted patterning of vertically aligned carbon nanotubes onto polymer substrates (2006)

This paper presents a low pressure hot embossing method for transferring patterns of vertically aligned carbon nanotubes into thermoplastic substrates. The procedure utilizes the synthesis of carbon nanotubes in discrete patterns on silicon substrates through the vapor liquid solid growth mechanism. The nanotube pattern and silicon stamp is placed on top of a polycarbonate film and locally heated above the glass transition temperature using microwave processing. The weight of the silicon substrate presses the nanotubes into the polycarbonate, resulting in the complete transfer of vertically aligned patterns. The technique is a rapid processing method, which could be used to integrate aligned nanomaterials with MEMS and flexible electronics that are fabricated on a wide range of thermoplastic polymer materials.
E-Textile Based Automatic Activity Diary for Medical Annotation and Analysis (2006)

Health monitoring applications often require that the patient maintain a diary of activities so that the physiological data can be correlated to what the user was doing. However, patients are notoriously bad at self-reporting. Consequently, it would be beneficial to automatically generate an activity diary. This paper presents a proof-of-concept prototype electronic textile system for recording both physiological data and context information. It also presents some of the issues that arise in the design and use of a health monitoring and activity annotation system
Relative Efficacy of Long-Acting Stimulants on Children With Attention Deficit-Hyperactivity Disorder: A Comparison of Standard Methylphenidate, Sustained-Release Methylphenidate, Sustained-Release Dextroamphetamine, and Pemoline (1990)

Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind, placebo-controlled, crossover evaluation of the efficacy of standard methylphenidate twice a day and comparable doses every morning of a sustained-release preparation of methylphenidate (SR-20 Ritalin), a sustained-release form of dextroamphetamine (Dexedrine Spansule), and pemoline. The children were participating in a summer treatment program in which they engaged in recreational and classroom activities. Dependent measures include evaluations of social behavior during group recreational activities, classroom performance, and performance on a continuous performance task. Results revealed generally equivalent and beneficial effects of all four medications. Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication. The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion, and the effects lasted for 9 hours. The implications of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed.