gebhart/patrepeval huggingface dataset:
Withdrawal Therapy Improves Chronic Daily Headache Associated with Long-Term Misuse of Headache Medication: A Retrospective Study (2000)

Chronic daily headache (CDH) associated with long-term misuse of headache medication is a common clinical problem which is refractory to most treatments. The present study is a retrospective analysis of the effect of drug withdrawal therapy in patients with CDH and frequent long-term use of headache symptomatic medication. One hundred and one adult patients (74 women and 27 men, aged between 16 and 72 years, mean age 43 years) were evaluated 1-3 months after drug withdrawal therapy had been initiated. The mean headache frequency at baseline was 26.9+/-4.0 days per month. Fifty-seven (56%) patients were significantly improved (defined as at least 50% reduction in number of headache days) after a period of drug withdrawal therapy. Based on the outcome of the drug withdrawal therapy, the patients were divided into three categories: group I, those who had between 0 and 10 headache days per month (n = 41), group II, those who had 11-20 days (n = 37), and group III, those who had 21-30 days (n = 23). The mean headache frequencies in groups I, II and III were 5.6+/-2.8 days, 15.7+/-2.5 days and 28.7+/-2.4 days, respectively. Treatment with amitriptyline was offered to patients in whom no improvement had been achieved. Ten of those 22 patients (36%) experienced a significant (> or = 50%) reduction of headache days. It is concluded that out-patient drug withdrawal therapy is the treatment of choice in patients with CDH and frequent long-term use of headache symptomatic medication, and that about one quarter of these CDH patients do not respond to drug withdrawal therapy only.
Retrovirus-Mediated Gene Transfer into Salivary Glands In Vivo (1996)

In the present report, we show prolonged expression of beta-galactosidase (beta-Gal) in the acinar cells of the submandibular and sublingual glands of rats following retrograde ductal injection of the retroviral vector BAG. To facilitate integration of viral DNA, cell division in the gland was induced by the administration of the beta-adrenergic agonist isoproterenol prior to the delivery of the vector. The frequency of cells stained for beta-Gal was higher if the virus was injected 4-20 hr after the two injections of isoproterenol given 24 hr apart than after the injection of only one dose of the drug. Without stimulation of cell division, no integration of the viral DNA was observed. Expression of the marker enzyme was observed up to 43 days, the limit of the observation period. The data indicate that salivary glands are potential targets of retrovirus-mediated gene transfer for somatic gene therapy.
Broadly Neutralizing Antibody‐Guided Carbohydrate‐Based HIV Vaccine Design: Challenges and Opportunities (2016)

The HIV envelope (Env) is heavily glycosylated, facilitating the spread and survival of HIV in many ways. Some potent broadly neutralizing antibodies (bnAbs) such as 2G12, PG9, PG16, and PGTs can recognize the conserved glycan residues on Env. The bnAbs, which often emerge after many years of chronic infection, provide insight into the vulnerability of HIV and can therefore guide the design of vaccines. Many carbohydrate-conjugated vaccines have been designed to induce bnAb-like antibodies, but none have yet been successful. The low antigenicity of these vaccines is one possible explanation. New strategies have been applied to obtain high-affinity antigens of glycan-dependent and other bnAbs. However, when used as immunogens in vivo, high-affinity antigens are still insufficient in eliciting bnAb-like antibodies. bnAbs generally possess some unusual features and may therefore be suppressed by the host immune system. In view of this situation, some immunization regimens based on the affinity maturation of antibodies have been tested. Herein we summarize recent studies into the design of carbohydrate-based HIV vaccines and some valuable experiences gained in work with other bnAb-based HIV vaccines.
QUADRATIC PROGRAMMING SOLUTION OF DYNAMIC MATRIX CONTROL (QDMC) (1986)

Abstract QDMC is an improved version of Shell's Dynamic Matrix Control (DMC) multivariable algorithm which provides a direct and efficient method for handling process constraints. The algorithm utilizes a quadratic program to compute moves on process manipulated variables which keep controlled variables close to their targets while preventing violations of process constraints. Several on-line applications have demonstrated its excellent constraint handling properties, transparent tuning and robustness, while requiring minimal on-line computational load. KEYWORDS: ConstraintsDynamic Matrix Control (DMC) Model-Predictive ControlMultivariable ControlQuadratic Programming (QP)
Preparation of Biotinylated Lectins and Application in Microtiter Plate Assays and Western Blotting (1996)

The biotinylation of lectins via amino groups with biotinamidocaproate N-hydroxysuccinimide ester provided reagents with fully preserved carbohydrate-binding activity which were detectable with high sensitivity using enzyme-conjugated ExtrAvidin. Lectins biotinylated with biotin hydrazide via periodate-oxidized carbohydrate residues were less sensitive reagents in avidin-mediated assays; however, the latter method may serve for identification of the lectin glycosylation status. The biotin/avidin-mediated lectin microtiter plate assay is described. Due to the high affinity of biotin-avidin interaction, this assay enables a more accurate determination of the lectin bound to the ligand-coated plate than an antibody-mediated, enzyme-linked immunosorbent assay (ELISA). The application of biotinylated lectins for detection of glycoproteins on the blot is also described and illustrated with several examples.
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis (2004)

The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. The novel bi-aryl urea BAY 43-9006 is a potent inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Additional characterization showed that BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrated significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor beta, Flt-3, and c-KIT. In cellular mechanistic assays, BAY 43-9006 demonstrated inhibition of the mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non-small-cell lung cancer cell lines expressing mutant KRAS were insensitive to inhibition of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition of VEGFR-2, platelet-derived growth factor receptor beta, and VEGFR-3 cellular receptor autophosphorylation was also observed for BAY 43-9006. Once daily oral dosing of BAY 43-9006 demonstrated broad-spectrum antitumor activity in colon, breast, and non-small-cell lung cancer xenograft models. Immunohistochemistry demonstrated a close association between inhibition of tumor growth and inhibition of the extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation in two of three xenograft models examined, consistent with inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional analyses of microvessel density and microvessel area in the same tumor sections using antimurine CD31 antibodies demonstrated significant inhibition of neovascularization in all three of the xenograft models. These data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis.
Characteristic Impedance Design Considerations for a High-Speed Superconducting Packaging System (Short Papers) (1985)

The characteristic impedance influences of superconducting packaging systems (in particular, Josephson packaging) on the degradation in transmitted signal rise time, amplitude distortions and crosstalk, signal propagation delay, and amplitude decay at the inductive and resistive connectors with matched capacitors are quantitatively evaluated by using the ASTAP computer simulation. The present choice of the characteristic impedance Z/sub 0/ = 10- 12 Omega for a superconducting stripline is inadequate. Higher impedances of Z/sub 0/=40-50 Omega are useful from the standpoint of noise performance improvement. At the same time, a higher impedance choice can make the ground connector numbers of each connector decrease, which is preferable for a large-scale packaging system.
Polyimide membrane with ZnO piezoelectric thin film pressure transducers as a differential pressure liquid flow sensor (2003)

Fabrication and characterization of ZnO thin film piezoelectric sensors on a polyimide membrane is presented in this paper. As a test device a differential pressure liquid flow sensor has been fabricated. We discuss new material combinations for the fabrication of the test devices. The pressure sensor membrane is a thin polyimide sheet bonded to a silicon wafer and the sensing material is sputtered ZnO piezoelectric thin film. The fabricated liquid flow sensor has been tested with a piezoelectric micropump for flow rates from 30 Î¼l h-1 to 300 Î¼l h-1 . Stroke volumes of 1 to 10 nl have been measured. The strain in the sensing layer has been modeled and a transverse piezoelectric coefficient of e31,f= -0.294 C m-2 has been extracted.
Sensitivity to Changes in the Intensity of White Noise and Its Relation to Masking and Loudness (1947)

Sensitivity to changes in the intensity of a random noise was determined over a wide range of intensities. The just detectable increment in the intensity of the noise is of the same order of magnitude as the just detectable increment in the intensity of pure tones. For intensities more than 30 db above the threshold of hearing for noise the size in decibels of the increment which can be heard 50 percent of the time is approximately constant (0.41 db). When the results of the experiment are regarded as measures of the masking of a noise by the noise itself, it can be shown that functions which describe intensity discrimination also describe the masking by white noise of pure tones and of speech. It is argued, therefore, that the determination of differential sensitivity to intensity is a special case of the more general masking experiment. The loudness of the noise was also determined, and just noticeable differences are shown to be unequal in subjective magnitude. A just noticeable difference at a low intensity produces a much smaller change in the apparent loudness than does a just noticeable difference at a high intensity.
Rigorous electromagnetic simulation applied to alignment systems (2001)

Rigorous electromagnetic simulation with TEMPEST is used to provide benchmark data and understanding of key parameters in the design of topographical features of alignment marks. Periodic large silicon trenches are analyzed as a function of wavelength (530-800 nm), duty cycle, depth, slope and angle of incidence. The signals are well behaved except when the trench width becomes about 1 micrometers or smaller. Segmentation of the trenches to form 3D marks shows that a segmentation period of 2-5 wavelengths makes the diffraction in the (1,1) direction about 1/3 to 1/2 of that in the main first order (1,0). Transmission alignment marks nanoimprint lithography using the difference between the +1 and -1 reflected orders showed a sensitivity of the difference signal to misalignment of 0.7%/nm for rigorous simulation and 0.5%/nm for simple ray-tracing. The sensitivity to a slanted substrate indentation was 10 nm off-set per degree of tilt from horizontal.
The luxS gene is involved in cell–cell signalling for toxin production in Clostridium perfringens (2002)

A Gram-positive anaerobic pathogen, Clostridium perfringens, causes clostridial myonecrosis or gas gangrene in humans by producing numerous extracellular toxins and enzymes that act in concert to degrade host tissues. C. perfringens possesses a homologue of the luxS gene that is reported to be responsible for the production of autoinducer 2 (AI-2), which participates in quorum sensing in bacteria. The luxS mutant was constructed using C. perfringens strain 13, and the role of the luxS gene in toxin production was examined. The cell-free culture supernatant from wild-type strain 13 greatly stimulated the luminescence of Vibrio harveyi BB170, whereas that from the luxS mutant caused no significant stimulation, indicating that the luxS gene is necessary for AI-2 production in C. perfringens. The luxS mutant showed a reduced level of production of alpha-, kappa- and theta-toxins. In the luxS mutant, the transcription of the theta-toxin gene (pfoA) was lower at mid-exponential growth phase, whereas alpha- and kappa-toxin gene transcription was not significantly affected. The production of toxins in the luxS mutant was stimulated by the addition of the culture supernatant from the wild-type cells, possibly because of the presence of AI-2. Moreover, the expression of the pfoA gene in the luxS mutant was apparently activated when the mutant cells were cultured in the presence of culture supernatants from the wild-type C. perfringens, Escherichia coli DH5alpha carrying the luxS gene of C. perfringens. A deletion analysis of the luxS operon showed that the luxS gene alone is responsible for cell-cell signalling, and that the metB or cysK genes located upstream of luxS are not involved in regulating toxin production. Our results indicate that cell-cell signalling by AI-2 plays an important role in the regulation of toxin production in C. perfringens.
Biophysical Characterization of Fungal Phytases ( myo -Inositol Hexakisphosphate Phosphohydrolases): Molecular Size, Glycosylation Pattern, and Engineering of Proteolytic Resistance (1999)

Phytases (myo-inositol hexakisphosphate phosphohydrolases) are found naturally in plants and microorganisms, particularly fungi. Interest in these enzymes has been stimulated by the fact that phytase supplements increase the availability of phosphorus in pig and poultry feed and thereby reduce environmental pollution due to excess phosphate excretion in areas where there is intensive livestock production. The wild-type phytases from six different fungi, Aspergillus niger, Aspergillus terreus, Aspergillus fumigatus, Emericella nidulans, Myceliophthora thermophila, and Talaromyces thermophilus, were overexpressed in either filamentous fungi or yeasts and purified, and their biophysical properties were compared with those of a phytase from Escherichia coli. All of the phytases examined are monomeric proteins. While E. coli phytase is a nonglycosylated enzyme, the glycosylation patterns of the fungal phytases proved to be highly variable, differing for individual phytases, for a given phytase produced in different expression systems, and for individual batches of a given phytase produced in a particular expression system. Whereas the extents of glycosylation were moderate when the fungal phytases were expressed in filamentous fungi, they were excessive when the phytases were expressed in yeasts. However, the different extents of glycosylation had no effect on the specific activity, the thermostability, or the refolding properties of individual phytases. When expressed in A. niger, several fungal phytases were susceptible to limited proteolysis by proteases present in the culture supernatant. N-terminal sequencing of the fragments revealed that cleavage invariably occurred at exposed loops on the surface of the molecule. Site-directed mutagenesis of A. fumigatus and E. nidulans phytases at the cleavage sites yielded mutants that were considerably more resistant to proteolytic attack. Therefore, engineering of exposed surface loops may be a strategy for improving phytase stability during feed processing and in the digestive tract.
Using graphic turing tests to counter automated DDoS attacks against web servers (2003)

We present WebSOS, a novel overlay-based architecture that provides guaranteed access to a web server that is targeted by a denial of service (DoS) attack. Our approach exploits two key characteristics of the web environment: its design around a human-centric interface, and the extensibility inherent in many browsers through downloadable "applets." We guarantee access to a web server for a large number of previously unknown users, without requiring pre-existing trust relationships between users and the system.Our prototype requires no modifications to either servers or browsers, and makes use of graphical Turing tests, web proxies, and client authentication using the SSL/TLS protocol, all readily supported by modern browsers. We use the WebSOS prototype to conduct a performance evaluation over the Internet using PlanetLab, a testbed for experimentation with network overlays. We determine the end-to-end latency using both a Chord-based approach and our shortcut extension. Our evaluation shows the latency increase by a factor of 7 and 2 respectively, confirming our simulation results.
Long-Term Results of External Upper Esophageal Sphincter Myotomy for Oropharyngeal Dysphagia (2009)

The aim of this work was to assess the efficacy of external myotomy of the upper esophageal sphincter (UES) for oropharyngeal dysphagia. In the period 1991-2006, 28 patients with longstanding dysphagia and/or aspiration problems of different etiologies underwent UES myotomy as a single surgical treatment. The main symptoms were difficulties in swallowing of a solid-food bolus, aspiration, and recurrent incidents of solid-food blockages. Pre- and postoperative manometry and videofluoroscopy were used to assess deglutition and aspiration. Outcome was defined as success in the case of complete relief or marked improvement of dysphagia and aspiration and as failure in the case of partial improvement or no improvement. Initial results showed success in 21 and failure in 7 patients. The best outcomes were observed in patients with dysphagia of unknown origin, noncancer-related iatrogenic etiology, and neuromuscular disease. No correlation was found between preoperative constrictor pharyngeal muscle activity and success rate. After follow-up of more than 1 year, 20 patients were marked as success and 3 as failure. All successful patients had full oral intake with a normal bolus consistency without clinically significant aspiration. We conclude that in select cases of oropharyngeal dysphagia success may be achieved by UES myotomy with restoration of oral intake of normal bolus consistency.
Serotonin as a mediator of cyclic flow variations in stenosed canine coronary arteries. (1986)

The data obtained in this study demonstrate that the concentration of serotonin is markedly elevated (18- to 27-fold) at the site of a coronary arterial stenosis in open-chest, anesthetized dogs with cyclic flow variations. Cyclic flow variations in this experimental preparation were abolished by ketanserin, a 5-hydroxytryptamine antagonist, but serotonin concentration at the site of the coronary stenosis remained elevated. The intra-atrial administration of serotonin (0.16 to 1 mg/min) restored cyclic flow variations after they had been abolished by ketanserin. Taken together, these data suggest that serotonin may be one of the important mediators of cyclic flow variations in this experimental preparation.
Minding Our Therapeutic Conversations: Meaning Bits and Choreographies (2006)

Postmodern approaches to therapy have been greatly informed by developments in social constructionist theory. Paralleling these innovations have been similarly informed developments in qualitative research, particularly in discourse analysis. For its attention to the taken-for-granted and microdynamic aspects of conversation, discourse analysis can help therapists better attune to their primary activity: constructively talking with clients. This article highlights some discursive “whats” and “hows” that can serve as signposts for therapists in minding their part in therapeutic dialogue with clients.
Advances in understanding the pathophysiology of headache. (1992)

Recent evidence suggests that migraine may not be due to vasoconstriction followed by reactive vasodilation, and tension-type headache may not be due to excess muscle contraction. The prodromes of migraine may have a hypothalamic origin, and the aura and changes in cognition may have a cortical neuronal origin. The pain of migraine and tension-type headache may be generated centrally or enhanced or generated by neurogenic inflammation. Drugs used to treat headache frequently interact with serotonin receptor subtypes: abortive drugs at the 5-HT1 receptor and preventive drugs at the 5-HT2 receptor.
Improved InGaP/GaAs HBTs AC performance and linearity with collector design (2004)

An additional thin high-doping layer within the collector of InGaP/GaAs HBTs has been designed and fabricated to improve the Kirk effect threshold current, cutoff frequency, and power distortion, while keeping a high breakdown voltage. The proposed structure effectively relieves the Kirk effect and results in a higher current drive and cut-off frequency. From the extracted C/sub BC/ with V/sub CB/, HBTs with non-uniform collector doping demonstrate less base-collector capacitance variation than that in baseline HBTs, due to the depletion region limited by the thin, high-doping layer. The experimental results on third-order intermodulation demonstrate a significant improvement in OIP3 by as large as 6 dB. This proposed InGaP/GaAs HBT, with non-uniform collector doping, is well suited to replace current InGaP/GaAs HBTs for power amplifier applications, due to its significantly improved linearity and current/frequency capability, with negligible impact on DC characteristics and fabrication.
Mapping the Anthrax Protective Antigen Binding Site on the Lethal and Edema Factors (2002)

Entry of anthrax edema factor (EF) and lethal factor (LF) into the cytosol of eukaryotic cells depends on their ability to translocate across the endosomal membrane in the presence of anthrax protective antigen (PA). Here we report attributes of the N-terminal domains of EF and LF (EF(N) and LF(N), respectively) that are critical for their initial interaction with PA. We found that deletion of the first 36 residues of LF(N) had no effect on its binding to PA or its ability to be translocated. To map the binding site for PA, we used the three-dimensional structure of LF and sequence similarity between EF and LF to select positions for mutagenesis. We identified seven sites in LF(N) (Asp-182, Asp-187, Leu-188, Tyr-223, His-229, Leu-235, and Tyr-236) where mutation to Ala produced significant binding defects, with H229A and Y236A almost completely eliminating binding. Homologous mutants of EF(N) displayed nearly identical defects. Cytotoxicity assays confirmed that the LF(N) mutations impact intoxication. The seven mutation-sensitive amino acids are clustered on the surface of LF and form a small convoluted patch with both hydrophobic and hydrophilic character. We propose that this patch constitutes the recognition site for PA.