gebhart/patrepeval huggingface dataset:
Fremanezumab—A Humanized Monoclonal Anti-CGRP Antibody—Inhibits Thinly Myelinated (Aδ) But Not Unmyelinated (C) Meningeal Nociceptors (2017)

Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated in the pathophysiology of migraine headache, but its role in migraine is still equivocal. As a new approach to migraine treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed to reduce the availability of CGRP, and were found effective in reducing the frequency of chronic and episodic migraine. We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons. To investigate the basis for this selective inhibitory effect, and further explore the mechanism of action of CGRP-mAbs, we tested the effect of fremanezumab on the cortical spreading depression-evoked activation of mechanosensitive primary afferent meningeal nociceptors that innervate the cranial dura, using single-unit recording in the trigeminal ganglion of anesthetized male rats. Fremanezumab pretreatment selectively inhibited the responsiveness of Aδ neurons, but not C-fiber neurons, as reflected in a decrease in the percentage of neurons that showed activation by cortical spreading depression. These findings identify Aδ meningeal nociceptors as a likely site of action of fremanezumab in the prevention of headache. The selectivity in its peripheral inhibitory action may partly account for fremanezumab's selective inhibition of high-threshold, as a result of a predominant A-δ input to high-threshold neurons, but not wide dynamic-range dorsal horn neurons, and why it may not be effective in all migraine patients.<b>SIGNIFICANCE STATEMENT</b> Recently, we reported that humanized CGRP monoclonal antibodies (CGRP-mAbs) prevent activation and sensitization of high-threshold (HT) but not wide-dynamic range trigeminovascular neurons by cortical spreading depression (CSD). In the current paper, we report that CGRP-mAbs prevent the activation of Aδ but not C-type meningeal nociceptors by CSD. This is the first identification of an anti-migraine drug that appears to be selective for Aδ-fibers (peripherally) and HT neurons (centrally). As the main CGRP-mAb site of action appears to be situated outside the brain, we conclude that the initiation of the headache phase of migraine depends on activation of meningeal nociceptors, and that for selected patients, activation of the Aδ-HT pain pathway may be sufficient for the generation of headache perception.
A new perturbation method for measuring microwave fields in free space (1955)

A perturbation method for measuring free-space microwave fields is described. A short thin metal rod forms the perturbing element. In order to avoid confusing the reflection from this rod with unwanted reflection the rod is arranged to spin about an axis perpendicular to its length. The perturbation of the field at the source is therefore modulated at a characteristic frequency, and by using an a.c. amplifier, steady reflections can be eliminated. The apparatus described operates at a wavelength of about 3.2 cm. Experimental results are given which verify the theory for linearly polarized waves. Extension of the method to elliptically polarized waves is possible in principle, but inherent ambiguities may be troublesome in practice.
The Influence of Carbon Dioxide on Brain Activity and Metabolism in Conscious Humans (2010)

A better understanding of carbon dioxide (CO(2)) effect on brain activity may have a profound impact on clinical studies using CO(2) manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO(2), via inhalation of 5% CO(2), may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO(2)) by 13.4% ± 2.3% (N=14) and, furthermore, the CMRO(2) change was proportional to the subject's end-tidal CO(2) (Et-CO(2)) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO(2) inhalation.
On the Pedagogical Benefits of Using John Woo's The Killer as a Model of Rene Girard's Theory on Religion and Violence (2001)

When asked for their views on the relation between religion and violence in John Woo's The Killer, students in our religion and film class typically deny that such relations exist. Using René Girard's work on mimesis and sacrifice, we have argued that it is possible to see that religion and violence in Woo's film are virtually inextricable from one another. Because Girard's theories can clearly be criticized on their own account, and because their application to The Killer is not without problems, we have also used discussions of the film to raise general questions about the use of theory and the meaning of interpretation.
Holographic tomography in three-dimensional photoelasticity within the Born approximation (1992)

In this paper, a holographic tomography method for the reconstruction of the applied stress field in a three-dimensional (3-D) photoelastic object is presented based on the weak scattering approximation. The optical inhomogeneity and anisotropy in the object are caused by the applied stress field through the photoelastic effect. The method uses angular-diversity illumination with monochromatic plane waves and planar recording screens. Polarizations of wave fields are considered and used together with the equilibrium equations for uncoupling the components of the dyadic scattering function. In this method, the low-pass version of the 3-D stress dyadic field in a model is reconstructed in a nondestructive manner.
Metallization optimization for high efficiency silicon heterojunction solar cells using low-temperature paste screen printing (2013)

An efficiency over 21% for silicon heterojunction solar cells has been successfully achieved in the RD line at AU Optronics (AUO). The performance improvement is stemmed from good passivation quality of thin film amorphous silicon layers, refined TCO formation, together with the optimized metallization process. In this paper, we focus on the progress of the screen printing technology using low-temperature conductive paste. Extensive efforts have been taken to reduce the serial resistance of the metallization. The trade off between front metal grid shading and resistance is also taken care of. We applied power loss calculation to optimize the metal contacts for a given TCO sheet resistance. AUO's new test run shows more than 2.8% reduction of power loss, which equals 0.64% absolute efficiency gain compared to our old test run.
Size-independent spin switching field using synthetic antiferromagnets (2003)

The arrays of the synthetic antiferromagnetic (SyAF) patterned bits consisting of Co90Fe10 (t1nm)/Ru (d nm)/Co90Fe10 (t2 nm) were successfully fabricated with micron to submicron sizes and different aspect ratios. Magnetization switching field Hsw and magnetic domain structure were investigated using magneto-optical Kerr effect and magnetic force microscopy (MFM), respectively. It was demonstrated that the strongly AF-coupled SyAF with aspect ratio k=1 creates size-independent Hsw down to submicron sizes fabricated, which is understood by zero demagnetization field for k=1 and single domain structure, observed by MFM. The size-independent switching field demonstrates the predominance of the SyAF for spintronics devices, requiring a low switching field and stabilized single domain structure for small bit sizes such as ultrahigh density magnetic random access memories and spin transistors.
Impaired Integrin-mediated Adhesion and Signaling in Fibroblasts Expressing a Dominant-negative Mutant PTP1B (1998)

To investigate the role of nonreceptor protein tyrosine phosphatase 1B (PTP1B) in beta1-integrin- mediated adhesion and signaling, we transfected mouse L cells with normal and catalytically inactive forms of the phosphatase. Parental cells and cells expressing the wild-type or mutant PTP1B were assayed for (a) adhesion, (b) spreading, (c) presence of focal adhesions and stress fibers, and (d) tyrosine phosphorylation. Parental cells and cells expressing wild-type PTP1B show similar morphology, are able to attach and spread on fibronectin, and form focal adhesions and stress fibers. In contrast, cells expressing the inactive PTP1B have a spindle-shaped morphology, reduced adhesion and spreading on fibronectin, and almost a complete absence of focal adhesions and stress fibers. Attachment to fibronectin induces tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin in parental cells and cells transfected with the wild-type PTP1B, while in cells transfected with the mutant PTP1B, such induction is not observed. Additionally, in cells expressing the mutant PTP1B, tyrosine phosphorylation of Src is enhanced and activity is reduced. Lysophosphatidic acid temporarily reverses the effects of the mutant PTP1B, suggesting the existence of a signaling pathway triggering focal adhesion assembly that bypasses the need for active PTP1B. PTP1B coimmunoprecipitates with beta1-integrin from nonionic detergent extracts and colocalizes with vinculin and the ends of actin stress fibers in focal adhesions. Our data suggest that PTP1B is a critical regulatory component of integrin signaling pathways, which is essential for adhesion, spreading, and formation of focal adhesions.
Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS? (2003)

It is well established that axonal regeneration in the adult CNS is largely unsuccessful. Numerous axon-inhibitory molecules are now known to be present in the injured CNS, and various strategies for overcoming these obstacles and enhancing CNS regeneration have been experimentally developed. Recently, the use of chondroitinase-ABC to treat models of CNS injury in vivo has proven to be highly beneficial towards regenerating axons, by degrading the axon-inhibitory chondroitin sulphate glycosaminoglycan chains found on many proteoglycans in the astroglial scar. This enzyme has now been shown to restore synaptic plasticity in the visual cortex of adult rats by disrupting perineuronal nets, which contain high levels of chondroitin sulphate proteoglycans (CS-PGs) and are expressed postnatally around groups of certain neurons in the normal CNS. The findings suggest exciting prospects for enhancing growth and plasticity in the adult CNS; however, some protective roles of CS-PGs in the CNS have also been demonstrated. Clearly many questions concerning the mechanisms regulating expression of extracellular matrix molecules in CNS pathology remain to be answered.
Anomalous cytokeratin expression in malignant melanoma: one- and two-dimensional western blot analysis and immunohistochemical survey of 100 melanomas. (1990)

Immunohistochemical characterization is an accepted method of human cell typing and tumor diagnosis. The differentiation of undifferentiated carcinoma from amelanotic melanoma is usually achieved by demonstration of cytokeratin (CK) intermediate filaments in carcinoma but not in melanoma. In examination of 100 melanomas fixed in formalin or methacarn and frozen tissue sections, we have found CK-immunoreactivity in 2, 8, and 21% of cases, respectively, with multiple anticytokeratin antibodies displaying overlapping antigenic specificities. In addition, we have confirmed the anomalous expression of low molecular weight CK proteins by one- and two-dimensional gel electrophoresis and immunoblotting of extracts of an immunohistochemically positive case. This latter finding indicates that CK staining in melanomas reflects the presence of authentic CK peptides and is not an artefact induced by fixation or cross-reacting antibodies. These observations have direct implications for the application of immunohistochemistry to the present practice of diagnostic surgical pathology. The anomalous CK expression by melanoma limits the diagnostic reliability of immunohistochemically demonstrated CK alone to indicate a diagnosis of carcinoma, without the concomitant detection of additional tumor-associated antigens. The finding of anomalous CK expression only in metastatic or recurrent melanomas raises an interesting question of possible association with tumor progression.
A photopolymerizable glass with diffraction efficiency near 100% for holographic storage (2001)

Permanent holographic storage has been demonstrated in a photopolymerizable organically modified silica glass. The glass was prepared by dispersing a titanocene photoinitiator and a high refractive index acrylic monomer in a porous silica matrix. This glass exhibits unprecedented sensitivity and refractive index change upon a moderate exposure to green light and can be fabricated in thickness up to several millimeters. A photopolymerizable storage medium of such a thickness with good holographic properties is needed for practical holographic storage devices. Lack of such medium has been considered the main obstacle in development of write-once holographic memories. In our glass, we have stored permanent volume holograms of diffraction efficiency approaching 100% and refractive index modulation up to 4.5×10−3, making this photopolymerizable material suitable for use in holographic data storage.
Assignment of the Vascular Endothelial Growth Factor Gene to Human Chromosome 6p21.3 (1996)

The location of the VEGF gene in the 6p21.3 region is a potential starting point for a linkage study. In addition, the isolation of YAC clones containing the VEGF gene will contribute to the construction of the physical map of this chromosomal region.
Hordothionins inhibit protein synthesis at the level of initiation in the wheat‐germ system (1994)

The inhibitory effect of pure alpha and beta hordothionins on protein synthesis directed by pea mRNA has been studied in the wheat-germ translation system. It is demonstrated that a component of the wheat germ counteracts the thionin effect. Formation of polysomes in vitro in the presence of thionin was inhibited to the same extent as the total translation system while run-off translation of isolated polysomes from pea plants was not affected by thionin. These data are consistent with an effect of thionin on the initiation reaction. Analyses of the formation of initiation complexes in the presence and absence of mRNA support this view and show that thionin interferes with the formation of the 43S complex. In accordance with this observation and in contrast to earlier studies no evidence has been obtained for a direct interaction between mRNAs and thionins. The analysis of the translation products also gave no indication for preferential translation of individual mRNAs by the thionin-inhibited translation system. Compared to translation in vitro, exposure of barley protoplasts to thionins showed a less dramatic effect on protein synthesis as measured by incorporation of [35S]methionine into proteins. These data are discussed with respect to the effects of thionins on the plasma membranes as shown previously with animal cell cultures. It is concluded that at least in barley such effects would need higher concentrations of thionins than are required for the inhibition of protein synthesis.
Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase. (1998)

TER286 is a latent drug activated by human glutathione S-transferase (GST) isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609 human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human breast carcinoma, selected for resistance to cyclophosphamide, both showed increased sensitivity to TER286 over their parental lines in parallel with increased expression of GST P1-1. In primary human tumor clonogenic assays, the spectrum of cytotoxic activity observed for TER286 was both broad and unusual when compared to a variety of current drugs. In murine xenografts of M7609 engineered to have high, medium, or low GST P1-1, responses to TER286 were positively correlated with the level of P1-1. Cytotoxicity was also observed in several other cell culture and xenograft models. In xenografts of the MX-1 human breast carcinoma, tumor growth inhibition or regression was observed in nearly all of the animals treated with an aggressive regimen of five daily doses. This schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to 60% of control and was no worse than for a single dose of TER286. These studies have motivated election of TER286 as a clinical candidate.
Essential Protein-Protein Interactions between Plasmodium falciparum Thymidylate Synthase and Dihydrofolate Reductase Domains (1999)

In Plasmodium falciparum, dihydrofolate reductase and thymidylate synthase activities are conferred by a single 70-kDa bifunctional polypeptide (DHFR-TS, dihydrofolate reductase-thymidylate synthase) which assembles into a functional 140-kDa homodimer. In mammals, the two enzymes are smaller distinct molecules encoded on different genes. A 27-kDa amino domain of malarial DHFR-TS is sufficient to provide DHFR activity, but the structural requirements for TS function have not been established. Although the 3'-end of DHFR-TS has high homology to TS sequences from other species, expression of this protein fragment failed to yield active TS enzyme, and it failed to complement TS(-) Escherichia coli. Unexpectedly, even partial 5'-deletion of full-length DHFR-TS gene abolished TS function on the 3'-end. Thus, it was hypothesized that the amino end of the bifunctional parasite protein plays an important role in TS function. When the 27-kDa amino domain (DHFR) was provided in trans, a previously inactive 40-kDa carboxyl-domain from malarial DHFR-TS regained its TS function. Physical characterization of the "split enzymes" revealed that the 27- and the 40-kDa fragments of DHFR-TS had reassembled into a 140-kDa hybrid complex. Thus, in malarial DHFR-TS, there are physical interactions between the DHFR domain and the TS domain, and these interactions are necessary to obtain a catalytically active TS. Interference with these essential protein-protein interactions could lead to new selective strategies to treat malaria resistant to traditional DHFR-TS inhibitors.
Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. Definition of molecular abnormality in transthyretin (prealbumin). (1984)

Amyloid fibril protein in patients with familial amyloidotic polyneuropathy is known to be chemically related to transthyretin (TTR), the plasma protein that is usually referred to as prealbumin. A ge- netically abnormal TTR may be involved in this disease.
Vagus nerve stimulation and drug reduction (2001)

The authors prospectively assessed drug reduction and patient satisfaction in 21 patients using vagus nerve stimulation (VNS) for refractory epilepsy and compared results to a case-matched control group with a mean follow-up of 13.2 months. Significant antiepileptic drug (AED) reduction occurred in 9/21 (42.9%) of VNS patients averaging 0.43 AED/patient, with dose reduction in four patients (19.0%). For 12/21 (57.1%) patients not reducing AED, dose reduction occurred in 6/21 (28.6%). Drug and dose reduction of AED is possible in patients using VNS for refractory epilepsy without loss of seizure control and with improved patient satisfaction.
Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry (2001)

Anti-DNA autoantibodies are the hallmark of human and murine systemic lupus erythematosus (SLE), an autoimmune rheumatic disease of unknown etiology. Some of these antibodies are believed to be pathogenic for kidney tissue and to initiate immune glomerulonephritis. However, the mechanisms by which anti-DNA antibodies participate in tissue injury remain controversial. We have studied the in vivo pathogenicity of anti-DNA monoclonal antibodies in immune deficient mice, using a panel of murine B cell hybridomas. No consistent genetic or immunochemical differences were found between pathogenic and non-pathogenic anti-DNA antibodies. However, the two antibody populations differed in their cross-reaction with the acidic actin-binding protein, alpha-actinin, that is known to play a major role in the structural integrity of glomerular filtration components. These results suggest that kidney dysfunction in SLE may be facilitated by protein-nucleic acid antigenic mimicry.
[The DREZ lesion as an effective treatment for chronic hypothetically post-herpetic neuropathic pain. Case report and review of literature]. (2003)

The authors present a case of a 54-year-old woman with a 3-year history of chronic pain syndrome, probably of postherapeutic origin, with diffuse segmentary dermatome characteristics, both somatic and autonomic. The former were exemplified by a constant "burning" skin pain in the representation of Th8-LI dermatomes unilaterally, while the latter by a unilateral visceral pain within the abdominal cavity. Electrophysiological examination indicated a neuropathic origin of the pain, despite the lack of clinically evident sensory deficits and/or hypersensitivity. The pain was so intense that normal walking was difficult for the patient and ineffectiveness of her treatment made her suicidal. Since both pharmacological treatment (non-steroid analgesics, opioids, antidepressants, and anticonvulsants including gabapentin) and minimally invasive methods of treatment (blockades, thermolesions) failed to control pain, she was subjected to surgery. A right-sided DREZ lesion within the Th8-LI dermatomes resulted in a complete pain relief, both within the somatic and autonomic innervation projections, and in the patient's functional recovery.
Beam Quality In High-Power Laser Amplification (1989)

In order to contribute to the development of a reliable criterion for beam quality characterization, a review of the commonly used criteria is done. Several meaningful experimental works using oscillator-amplifier configurations for high power industrial CO2 lasers, are analyzed. The influence of some forms of inhomogeneity on the beam quality, in an oscillator-amplifier configuration, has been also investigated through numerical methods.
Compte-rendu de la Commission Recherche du 23 septembre 2014 (2014)

Ou il est question de la mise en place de la commission consultative des doctorants contractuels. 2014 09 23 Compte rendu de la Commission Recherche par Agir annexe-1_commission-consultative-des-doctorants-contractuels