gebhart/patrepeval huggingface dataset:
Towards a new kind of vaccine (2017)

Abstract We present new data showing that normal IgG immune responses comprise the production of two kinds of antibodies, namely anti-foreign and anti-anti-self antibodies. For example, immunization of C3H mice by two rounds of BL/6 skin grafting results in the production of anti-BL/6 antibodies plus antiidiotypic antibodies (C3H anti-anti-C3H) with the latter being detected using antibodies produced in a BL/6 anti-C3H immune response. Similarly, the IgG immune response of C3H mice to tetanus toxoid includes the production of C3H anti-anti-C3H antibodies. Antigen-specific antibodies produced in one alloimmunization plus antiidiotypic antibodies produced in the converse immunization can be used to synergistically induce specific tolerance. We show that infusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppress an immune response to BL/6 lymphocytes in C3H mice. Specific tolerance was measured as suppression of the induction of BL/6-specific cytotoxic T cells. The two kinds of antibodies with complementary specificity are believed to stimulate two populations of T lymphocytes, and co-selection (mutual selection) of these two populations leads to a new stable steady state of the system that has specifically diminished reactivity to BL/6 tissue. Stimulation with a combination of anti-C3H and C3H anti-anti-C3H IgG antibodies furthermore down-regulates inflammation in a mouse model of inflammatory bowel disease. An analogous combination of C3H anti-BL/6 and BL/6 anti-anti-BL/6 antibodies significantly down-regulates tumour growth and metastases in BALB/c mice in the EMT6 transplantable breast cancer model. We conclude that a combination of certain antigen-specific and antiidiotypic antibodies has potential as a new class of vaccines based on the symmetrical immune network theory. This new kind of vaccine does not involve the production of antibodies. The prevention of two important degenerative diseases makes this a potential anti-aging technology.
Contribution of postsynaptic T‐type calcium channels to parallel fibre‐Purkinje cell synaptic responses (2015)

In the cerebellum, sensory information is conveyed to Purkinje cells (PC) via the granule cell/parallel fibre (PF) pathway. Plasticity at the PF-PC synapse is considered to be a mechanism of information storage in motor learning. The induction of synaptic plasticity in the cerebellum and elsewhere usually involves intracellular Ca(2+) signals. Unusually, postsynaptic Ca(2+) signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca(2+) -impermeable; postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid Ca(2+) signalling mechanism. Low-threshold activated T-type calcium channels are present at the synapse, although their contribution to PF-PC synaptic responses is unknown. Taking advantage of 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide, a selective T-type channel antagonist, we show in the mouse that inhibition of these channels reduces PF-PC excitatory postsynaptic currents and excitatory postsynaptic potentials by 15-20%. This contribution was preserved during sparse input and repetitive activity. We characterized the biophysical properties of native T-type channels in young animals and modelled their activation during simulated dendritic excitatory postsynaptic potential waveforms. The comparison of modelled and observed synaptic responses suggests that T-type channels only activate in spines that are strongly depolarized by their synaptic input, a process requiring a high spine neck resistance. This brief and local activation ensures that T-type channels rapidly deactivate, thereby limiting inactivation during repetitive synaptic activity. T-type channels are therefore ideally situated to provide synaptic Ca(2+) entry at PF-PC spines.
Verification experimentale de l'existence d'un gene a effet majeur sur la qualite de la carcasse chez le porc et recherche d'un locus marqueur facilitant son utilisation (1993)

"Chantier qualité spécifique "Auteurs Externes" département de Génétique animale : uniquement liaison auteur au référentiel HR-Access "
Local Strain, Structured Diffuse Scattering and Oxygen/Fluorine Ordering in Transition Metal Oxyfluorides (2004)

Conventional crystal structure refinements commonly report ‘random’ anion site occupancies for the anion, or X, site positions of many metal oxyfluoride phases despite compelling evidence suggesting there must exist at least local O/F ordering. Diffraction evidence for such local ordering has been found to exist in a range of oxyfluorides in the form of structured diffuse scattering, typically a consequence of the correlated displacive relaxation of the cations induced by local O/F ordering.
High resolution MRI of the brain at 4.7 Tesla using fast spin echo imaging (2003)

Over recent years, high field MR scanners (3 T and above) have become increasingly widespread due to potential advantages such as higher signal-to-noise ratio. However, few examples of high resolution images covering the whole brain in reasonable acquisition times have been published to date and none have used fast spin echo (FSE), a sequence commonly employed for the acquisition of T(2) weighted images at 1.5 T. This is mostly due to the increased technical challenges associated with uniform signal generation and the increasingly restrictive constraints of current safety guidelines at high field. We investigated 10 volunteers using an FSE sequence optimized to the 4.7 T environment. This sequence allows the acquisition of 17- and 34-slice data sets with an in-plane resolution of approximately 500 microm x 500 microm and a slice thickness of 2 mm, in 5 min 40 s and 11 min 20 s, respectively. The images appear T(2) weighted, although the contrast is due to the combined effects of chosen echo time, magnetization transfer, direct radio frequency saturation and diffusion as well as the T(1) and T(2) relaxation times of the tissue. The result is an excellent detailed visualization of anatomical structures, demonstrating the great potential of 4.7 T MRI for clinical applications. This paper shows that, with careful optimization of sequence parameters, FSE imaging can be used at high field to generate images with high spatial resolution and uniform contrast across the whole brain within the prescribed power deposition limits.
Analysis of DNA-Guided Self-Assembly of Microspheres Using Imaging Flow Cytometry (2012)

Imaging flow cytometry was used to analyze the self-assembly of DNA-conjugated polystyrene microspheres. This technique enables quantitative analysis of the assembly process and thereby enables detailed analysis of the effect of structural and process variables on the assembly yield. In a demonstration of the potential of this technique, the influence of DNA strand base pair (bp) length was examined, and it was found that 50 bp was sufficient to drive the assembly of microspheres efficiently, forming not only dimers but also chainlike structures. The effect of stoichiometry on the yield was also examined. The analysis demonstrated that self-assembly of 50 bp microspheres can be driven nearly to completion by stoichiometric excess in a manner similar to Le Chatelier's principle in common chemical equilibrium.
Inheritance of Unequal Numbers of the Genes Encoding the Human Neutrophil Defensins HP-1 and HP-3 (1995)

It is unclear whether the six known human defensin peptides are all encoded by separate genes or whether some of them are allelic. Three of the peptides, HP-1, HP-2, and HP-3, differ by only one amino acid, and it is thought that HP-2 may represent a proteolytic product of HP-1 and/or HP-3. To help determine the relationship of these three proteins, we isolated a nearly full-length cDNA encoding HP-1 with a sequence very similar to, but different from, the previously isolated HP-1 and -3 cDNAs. Gene copy number experiments established that there were at least two but fewer than five defensin genes with a high level of similarity to the HP-1 cDNA (HP-1/3-like). Three genomic clones were isolated that contained two different configurations of the HP-1/3-like sequences. Sequencing established that one encoded the HP-1 peptide, whereas the other encoded HP-3. Analysis of DNAs obtained from 18 unrelated individuals by Southern blot analysis revealed the expected fragments as well as additional fragments that were not present in the genomic clones. This suggested the possibility of alleles; however, when DNAs from families were examined, these fragments did not segregate in an obvious Mendelian fashion. The HP-1/3-like defensin genes are on human chromosome 8. Surprisingly, somatic cell hybrid mapping showed that the number of HP-1/3-like genes on isolated copies of chromosome 8 was variable. We conclude that individuals can inherit versions of chromosome 8 harboring either two or three copies of the genes that encode the HP-1, HP-2, and/or HP-3 peptides.
ChemInform Abstract: Chemistry of Opium Alkaloids. Part 27. Diene Systems in N‐Formylmorphinans. Formation of a Dibenz(d,f)azonine: A New Example of Molecular Acrobatics in Morphinans. (1989)

Abstract A new synthesis of 6‐demethoxy‐N‐formyl‐N‐northebaine (VI) starts from codeine (Ia) via the intermediates shown in the scheme.
Evaluating first seizures in adults in primary care. (2011)

A seizure is defined as the clinical manifestation resulting from an excessive and abnormal discharge of a population of neurones. The individual lifetime risk of developing a non-febrile seizure is about 5% and around a third of patients will experience further seizures and be diagnosed as having epilepsy. When assessing a possible first seizure, assuming that the patient has recovered and is not in an emergency situation, the first question is whether the paroxysmal event was a seizure. There are many seizure imitators, some of which can be fatal if missed. These include cardiac syncope due to arrhythmias, valvular abnormalities or ischaemia, hypotension, hypoglycaemia and TIAs. Ultimately, the diagnosis of a seizure is clinical and is best established by taking an accurate history. An accurate description of the paroxysmal event is paramount. So the patient should ideally bring a witness to the consultation, allow the clinician to contact a witness by phone, or provide a written description of the paroxysm. Further features to be established include type of seizure (generalised or partial) and timing (early morning or nocturnal). The past medical history should be probed for previous syncopal events or possible seizures. Once a putative diagnosis of a seizure has been made, the second question is whether the seizure was provoked or not. Examination should include assessment of the level of consciousness and orientation, and the cardiovascular and nervous systems. In the patient who has fully recovered from a first seizure NICE recommends measuring plasma glucose, and electrolytes including calcium, and a 12-lead ECG. Referral to an emergency department for urgent neuroimaging and lumbar puncture should be considered if the patient has not fully recovered, and/or if risk factors are present. If the patient has fully recovered, guidelines recommend referral to a first seizure clinic for review by an epilepsy specialist.
Kieferbeschwerden aus Sicht des Fasziendistorsionsmodells (FDM) (2011)

Das Fasziendistorsionsmodell (FDM) kennt verschiedene, prinzipiell reversible Fasziendistorsionen, die einzeln oder in Kombination ursächlich für Schmerzzustände und körperliche Beschwerden verantwortlich sind. Auch bei Problemen im Bereich des Kiefers können Fasziendistorsionen anhand der Körpersprache und der Aussagen der Patienten identifiziert und spezifisch behandelt werden.
Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors (2017)

Influenza polymerase uses short capped primers snatched from nascent Pol II transcripts to initiate transcription of viral mRNAs. Here we describe crystal structures of influenza A and B polymerase bound to a capped primer in a configuration consistent with transcription initiation ('priming state') and show by functional assays that conserved residues from both the PB2 midlink and cap-binding domains are important for positioning the capped RNA. In particular, mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap, significantly and specifically decreases cap-dependent transcription. We also compare the configuration of the midlink and cap-binding domains in the priming state with their very different relative arrangement (called the 'apo' state) in structures where the potent cap-binding inhibitor VX-787, or a close analogue, is bound. In the 'apo' state the inhibitor makes additional interactions to the midlink domain that increases its affinity beyond that to the cap-binding domain alone. The comparison suggests that the mechanism of resistance of certain mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA binding as well as stabilization of the transcriptionally inactive 'apo' state.
Unsteady Aerodynamic Measurements on a Rotating Compressor Blade Row at Low Mach Number (1987)

An experiment was conducted on a heavily instrumented isolated model compressor rotor to study the unsteady aerodynamic response of the blade row to a controlled pitching oscillation of all blades in an undistorted flow, and to a circumferential inlet flow distortion with nonoscillating blades. To accomplish this, miniature pressure transducers were embedded in the blades and the unsteady pressure time histories were recorded. Both phases of the experiment were performed over a wide range of flow coefficient, from Cx/Um = 0.6 to 0.95 in 0.05 steps, and data were taken at each condition for sinusoidal disturbances characterized by one, two, and four per revolution waves. Steady-state data were acquired for flow coefficients from 0.55 to 0.99 in 0.05 steps. In this paper the steady and unsteady results of the portion of this experiment dealing with oscillating blades are compared with analytical predictions, and the steady results are compared with experimental data from previous work. Although the model blades were instrumented at five spanwise stations, only the midspan measurements will be presented herein. The measured pressures for nonoscillating blades were in good agreement with the steady potential flow predictions (and with previous steady experimental data) when the measured exit angle was imposed as the downstream boundary condition for the analysis. It was found that a quasi-steady approach yielded marginally acceptable agreement with the experimental results for the lowest frequency tested. For the higher reduced frequencies, the experimental data could not be modeled in this manner. In contrast, a comparison of the measurements with the Verdon–Caspar unsteady potential flow theory produced generally good agreement except near the leading edge at high mean incidence (i.e., at low flow coefficient). At high incidence the blades in this experiment had very high steady pressure gradients near the leading edge and it is suspected that this may be responsible for the lack of agreement. The agreement was somewhat better at the higher frequencies.
ANALYSIS OF RADIATION EXPOSURES DURING 1962 (1963)

External radiation exposures received by Atomic Energy of Canada Limited workers in 1962 were analyzed by machine accounting methods. The data are presented. (auth)
Twenty-four-hour storage of kidneys (1969)

Abstract Canine kidneys have been preserved for twenty-four hours by one of four methods in an attempt to define a suitable technique for application to human cadaveric kidneys before transplantation. Hypothermia was common to all methods, being used alone, supplemented by hyperbaric oxygen or combined with continuous perfusion with 50% blood at 30 mm. Hg pressure in an environment of one or three atmospheres of oxygen. After storage, the kidney was reimplanted into the pelvis of the donor animal and contralateral nephrectomy was performed three weeks later. Consistently successful preservation was achieved by simple hypothermia. Hyperbaric oxygen conferred significant benefit as judged histologically and biochemically. Continuous perfusion was associated with vascular damage and poor subsequent function. In successful experiments long-term survival was obtained irrespective of the storage method used.
Letters (1960)

Letters Get access K. L. Jones, K. L. Jones Chairman Department of Botany, University of Michigan, Ann Arbor Search for other works by this author on: Oxford Academic Google Scholar Richard A. Edgren Richard A. Edgren Division of Biological Research, G. D. Searle & Co., Chicago, Illinois Search for other works by this author on: Oxford Academic Google Scholar AIBS Bulletin, Volume 10, Issue 3, June 1960, Pages 5–6, https://doi.org/10.2307/1292621 Published: 01 June 1960
EPR Spectroscopic Analysis of U7 Hammerhead Ribozyme Dynamics during Metal Ion Induced Folding (2005)

Electron paramagnetic resonance (EPR) spectroscopy was used to examine changes in internal structure and dynamics of the hammerhead ribozyme upon metal ion induced folding, changes in pH, and the presence and absence of ribozyme inhibitors. A nitroxide spin-label was attached to nucleotide U7 of the HH16 catalytic core, and this modified ribozyme was observed to retain catalytic activity. U7 was shown by EPR spectroscopy to be more mobile in the ribozyme-product complex than in either the unfolded ribozyme or the ribozyme-substrate complex. A two-step divalent metal ion dependent folding pathway was observed for the ribozyme-substrate complex with a weak first transition observed at 0.25 mM Mg2+ and a strong second transition observed around 10 mM Mg2+, in agreement with studies using other biophysical and biochemical techniques. Previously, ribozyme activity was observed in the absence of divalent metal ions and the presence of high concentrations of monovalent metal ions, although the activity was less than that observed in the presence of divalent metal ions. Here, we observed similar dynamics for U7 in the presence of 4 M Na+ or Li+, which were distinctively different than that observed in the presence of 10 mM Mg2+, indicating that U7 of the catalytic core forms a different microenvironment under monovalent versus divalent metal ion conditions. Interestingly, the catalytically efficient microenvironment of U7 was similar to that observed in a solution containing 1 M Na+ upon addition of one divalent metal ion per ribozyme. In summary, these results demonstrate that changes in local dynamics, as detected by EPR spectroscopy, can be used to study conformational changes associated with RNA folding and function.
Optische Längenmeßeinrichtung zur Messung des Abstandes zu einem Bezugsstrahl / An optical device for length measurement between a measuring point and a reference beam (1981)

Article Optische Längenmeßeinrichtung zur Messung des Abstandes zu einem Bezugsstrahl / An optical device for length measurement between a measuring point and a reference beam was published on December 1, 1981 in the journal tm - Technisches Messen (volume 48, issue JG).
Effects of Mutations at the <i>W</i> Locus (<i>c‐kit</i>) on Inner Ear Pigmentation and Function in the Mouse (1994)

The W locus encodes a tyrosine kinase receptor, c-kit, which affects survival of melanoblasts from the neural crest. The primary cochlear defect in Viable Dominant Spotting (Wv/Wv) mutants is a lack of melanocytes within the stria vascularis (SV) associated with an endocochlear potential (EP) close to zero and hearing impairment. In this study, we compare inner ear pigmentation with cochlear potentials in three other W alleles (Wx, Wsh, and W41) and reveal an unequivocal correlation between presence of strial melanocytes and presence of an EP. Asymmetry was common, and 8.3% of Wsh/Wx, 25% of Wsh/Wsh, 60% of W41/Wx, and 69.2% of W41/W41 ears had a pigmented stria and an EP, while the remainder had no strial melanocytes and no EP. In those mutants that partially escaped the effects of the mutation, strial melanocytes rarely extended the entire length of the stria, but were confined to the middle and/or basal turns of the cochlea. The extent of strial pigmentation was unrelated to the EP value, which was measured from the basal turn only. Compound action potential (CAP) responses recorded from ears with an EP were variable and they showed greatly raised thresholds or were absent in all ears where the EP was close to zero. In controls, melanocytes in the vestibular part of the ear were found in the utricle, crus commune, and ampullae, whereas in many mutants only one or two of these regions were pigmented. There was a broad correlation between pigmentation of the stria and pigmentation of the vestibular region but this was not absolute. All W41/Wx, Wsh/Wsh, and W41/W41 mutants had some pigment on the pinna but, in contrast to controls where melanocytes were found in the epidermis and dermis of the pinna, pigment cells were reduced in number and generally restricted to the dermis. Injection of normal neural crest cells into 9.5-day-old mutant embryos increased the extent of skin pigmentation on the head and coat of adult chimeras and was associated with a small increase in the proportion of pigmented strias.
Electronic Properties of Polysilanes (1995)

The results of recent studies of the electronic properties of polysilanes are reviewed. The electronic states can be described by the Hückel model if coulomb interactions are included using the Pariser-Parr-Pople approximation. The long polymer chains appear to be divided into random length, short, ordered segments by conformational defects, with the energy of the excited states depending on the length of the segments. In isolated polymer chains energy is transferred from high-energy, short segments to longer, lower energy segments but the distance and time during which transfers take place is very limited. In solid films the excitons become highly mobile and remain mobile throughout their lifetime, even at low temperatures. Holes are quite mobile in solid films and the characteristics of transport are the same as those of charge carrier transport in molecularly doped polymer films.
Diversification of an emerging pathogen in a biodiversity hotspot: <i><scp>L</scp>eptospira</i> in endemic small mammals of <scp>M</scp>adagascar (2014)

Biodiversity hotspots and associated endemism are ideal systems for the study of parasite diversity within host communities. Here, we investigated the ecological and evolutionary forces acting on the diversification of an emerging bacterial pathogen, Leptospira spp., in communities of endemic Malagasy small mammals. We determined the infection rate with pathogenic Leptospira in 20 species of sympatric rodents (subfamily Nesomyinae) and tenrecids (family Tenrecidae) at two eastern humid forest localities. A multilocus genotyping analysis allowed the characterization of bacterial diversity within small mammals and gave insights into their genetic relationships with Leptospira infecting endemic Malagasy bats (family Miniopteridae and Vespertilionidae). We report for the first time the presence of pathogenic Leptospira in Malagasy endemic small mammals, with an overall prevalence of 13%. In addition, these hosts harbour species of Leptospira (L. kirschneri, L. borgpetersenii and L. borgpetersenii group B) which are different from those reported in introduced rats (L. interrogans) on Madagascar. The diversification of Leptospira on Madagascar can be traced millions of years into evolutionary history, resulting in the divergence of endemic lineages and strong host specificity. These observations are discussed in relation to the relative roles of endemic vs. introduced mammal species in the evolution and epidemiology of Leptospira on Madagascar, specifically how biodiversity and biogeographical processes can shape community ecology of an emerging pathogen and lead to its diversification within native animal communities.