gebhart/patrepeval huggingface dataset:
Topiramate in the Treatment of Chronic Migraine (2003)

The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache +/- SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.
[Allergology in the year 2000]. (1994)

As already today, the use of fully standardized allergens for specific allergen phenotyping will be essential also in the future. The determination of allergen-reactive patterns in patients will be performed with panels of tracer allergens being produced by molecular biology techniques. Such recombinant allergen proteins can in principal also be used for specific immunotherapy. Undesired biological properties of allergens can be removed by directed mutagenesis. Because recombinant allergens can bind IgE only selectively, T-cell activating fragments thereof may be employed. This may lead to fully artificial protein constructs consisting of immunogenic and allergy-suppressing parts. A different possible way is the therapeutic use of immunologically active proteins, such as monoclonal antibodies or soluble receptors, which suppress IL-4 and/or IgE synthesis. The accessibility of these proteins will lead to a better understanding of the mechanisms responsible for the development of allergy. At the end of this development one could conceive the construction of low molecular chemical agents, drugs in the classical sense, able to regulate IgE synthesis. Of highest significance will be the establishment of genetic markers for atopy and allergy. Such genes may not only indicate a genetic predisposition for the disease but also open an immense spectrum of new diagnostic and therapeutic applications in allergy.
Aza-Claisen Rearrangements Initiated by Acid-Catalyzed Michael Addition (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAza-Claisen Rearrangements Initiated by Acid-Catalyzed Michael AdditionEdwin Vedejs and Marc GingrasCite this: J. Am. Chem. Soc. 1994, 116, 2, 579–588Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/ja00081a019https://doi.org/10.1021/ja00081a019research-articleACS PublicationsRequest reuse permissionsArticle Views1727Altmetric-Citations80LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Evaluation of Envelope Vaccines Derived from the South African Subtype C Human Immunodeficiency Virus Type 1 TV1 Strain (2005)

Human immunodeficiency virus type 1 (HIV-1) subtype C infections are on the rise in Sub-Saharan Africa and Asia. Therefore, there is a need to develop an HIV vaccine capable of eliciting broadly reactive immune responses against members of this subtype. We show here that modified HIV envelope (env) DNA vaccines derived from the South African subtype C TV1 strain are able to prime for humoral responses in rabbits and rhesus macaques. Priming rabbits with DNA plasmids encoding V2-deleted TV1 gp140 (gp140TV1DeltaV2), followed by boosting with oligomeric protein (o-gp140TV1DeltaV2) in MF59 adjuvant, elicited higher titers of env-binding and autologous neutralizing antibodies than priming with DNA vaccines encoding the full-length TV1 env (gp160) or the intact TV1 gp140. Immunization with V2-deleted subtype B SF162 env and V2-deleted TV1 env together using a multivalent vaccine approach induced high titers of oligomeric env-binding antibodies and autologous neutralizing antibodies against both the subtypes B and C vaccine strains, HIV-1 SF162 and TV1, respectively. Low-level neutralizing activity against the heterologous South African subtype C TV2 strain, as well as a small subset of viruses in a panel of 13 heterologous primary isolates, was observed in some rabbits immunized with the V2-deleted vaccines. Immunization of rhesus macaques with the V2-deleted TV1 DNA prime/protein boost also elicited high titers of env-binding antibodies and moderate titers of autologous TV1 neutralizing antibodies. The pilot-scale production of the various TV1 DNA vaccine constructs and env proteins described here should provide an initial platform upon which to improve the immunogenicity of these subtype C HIV envelope vaccines.
Concentration of Fetal Red Blood Cells From a Mixture of Maternal and Fetal Blood by Anti-i Serum—An Aid to Prenatal Diagnosis of Hemoglobinopathies (1974)

Abstract Fetal red blood cells were concentrated from mixtures of maternal and fetal cells by differential agglutination with anti-i serum. This method will be useful for prenatal diagnosis of hemoglobinopathies when blood obtained from the fetus is heavily contaminated by maternal cells. The method is practical, except in very rare cases in which the maternal red cells are strongly agglutinated by anti-i.
D2O to determine muscle protein synthesis rates in response to post‐exercise nutrition in adults (2010)

Muscle protein synthesis (MPS) is acutely stimulated by either endurance exercise or protein consumption, but the long‐term and combined effects in older adults are unknown. We used deuterium oxide (D 2 O) to evaluate long‐term effects of post‐exercise nutrition and endurance training on MPS. Sedentary adults (n=16, 50±8 yrs) performed 6‐wks of endurance training and consumed either a carbohydrate (CHO) or carbohydrate and protein (PRO) drink after exercise. D 2 O (50 ml tid) was administered during the training period to maintain body water pool enrichment at 1–2%. VO 2 max was measured pre‐ and post‐training as a surrogate for mitochondrial function. MPS over the 6‐wks was determined from total percipitable protein in a 10–20 mg muscle biopsy by gas chromatography‐mass spectroscopy. Training increased (p&lt;0.05) VO 2 max in the PRO (25.5 ± 4.2 to 28.1±3.9 ml/kg/min) but not in CHO group (31.1 ±7.1 to 32.5 ±9.1 ml/kg/min). MPS was not different between CHO and PRO groups (0.06 ± 0.004 vs. 0.05 ±0.003 %/day, p=0.23). Although MPS was not different between CHO and PRO, the VO 2 max increase with PRO suggests post‐exercise nutrition may impact aerobic training adaptations. Further analysis will evaluate long‐term mitochondrial proliferation. Our use of D 2 O provides novel insight into long‐term synthesis rates in aging humans. Funding from The Colorado Nutritional Research Unit.
Cytosafe<sup>PLUS</sup> A Workstation for Screening, Supervision, Reviewing, Quality Assurance and Education in Cytopathology (1996)

In pathology, the subjective cytologic and histologic diagnosis suffers from large observer variability. Effective methods of reducing the effects of this observer variability in cytologic diagnosis are close supervision of the diagnostic process and multiple screening by different observers of cases that have a higher risk of abnormalities as well as closely supervised follow-up procedures for early lesions. Accurate supervision of screening completeness has become possible with the development of computer programs and microscope instrumentation to register the path of the objective over the slide and therefore the fields that have been inspected by the screener (Axio-Home, Carl Zeiss, Oberkochen, Germany; Navigator, Becton Dickinson Cellular Imaging Systems, Leiden, the Netherlands). Based on these technologies, all objects of interest on the microscope slide are marked electronically, and the X,Y coordinates of these marks are stored in the computer. With these coordinates, a motor-driven microscope stage can be redirected to the selected objects, enabling the observer to quickly review the objects. The reviewer can thus reinspect cells or groups of cells, previously identified, in a much more accurate way than is presently possible, by marking objects of interest with ink dots. To these marked objects, specific diagnoses can be attached, as can comments or questions, which are also stored in the computer and are made part of the cytology report. After analysis, all marked objects can be relocated automatically with the help of the computer-directed microscope stage. Using this concept, a subsequent observer or a supervisor can easily and effectively reply to the remarks attached to these objects. It is also possible to reedit the comments made or to attach answers to specific questions. In an interobserver study, encompassing 50 cases of columnar cell abnormalities screened by five observers using the Navigator microscope stage and software, it proved possible to reduce reviewing time significantly. On the basis of marked cytologic characteristics discriminating cellular features in the diagnosis, endocervical columnar abnormalities could be identified. The coordinates of the objects of interest are made part of the laboratory record of the cytology findings (Cytosafe, Omnisys, Hoevelaken, the Netherlands). This development largely facilitates the review of previous findings when evaluating follow-up specimens. With the use of a Navigator motor-driven stage and CCD camera, microscope images can be made of the specimen under study. These images can be stored in the computer in a digitized format, labeled with their X,Y coordinates on the specimen. The CytosafePLUS workstation, encompassing the Navigator automated cell positioning system and CCD attachment, is a highly effective tool in cytologic screening, reviewing and reporting, in surveillance of follow-up, in intralaboratory and interlaboratory consultation, in cytology training, in proficiency testing and in quality assurance.
A Novel Conductive Polymer-Sulfur Composite Cathode Material for Rechargeable Lithium Batteries (2002)

Conductive polymer–sulfur composites have been reported as potential cathode materials for rechargeable batteries due to their structure, i.e., sulfur embedded in a conductive polymer host at molecular level (see Figure for a backscattered electron photograph). The low-cost, environmentally friendly sulfur composite has outstanding electrochemical properties and is, hence, a highly interesting material for the next generation of lithium batteries.
Soy isoflavones increase preprandial peptide YY (PYY), but have no effect on ghrelin and body weight in healthy postmenopausal women (2006)

Soy isoflavone supplementation for eight weeks did not significantly reduce energy intake or body weight, even though plasma PYY increased during isoflavone treatment. Ghrelin remained unaffected by isoflavone treatment. A larger and more rigorous appetite experiment might detect smaller differences in energy intake after isoflavone consumption. However, the results of the present study do not indicate that increased PYY has a major role in the regulation of body weight, at least in healthy postmenopausal women.
Bio Control Potential of Pseudomonas fluorescens against Coleus Root Rot Disease (2014)

Ten different strains of Pseudomonas fluorescens were isolated from coleus rhizosphere except the pf1 strain and identified by biochemical tests. These strains were screened against Macrophomina phaseolina (Tassi) Goid, the causal organism of coleus root rot. The results revealed that Pf1 strains recorded maximum inhibition of mycelial growth against control. The mechanism of Pseudomonas strains namely the iron-chelating agent (siderophore), volatiles (HCN) and antibiotic (Fluorescein and pyocyanin) production tests were studied and reacted for siderophore, antibiotic and HCN production. The talc-based formulation of Pf1 and CPF1 was prepared and the bio-efficacy was tested under greenhouse conditions. The stem cutting and soil application of the talc-based formulation of Pf1 significantly reduced the root rot incidence and increased shoot and tuber length also.
The inverse problem in electrocardiography: solutions in terms of equivalent sources. (1988)

This paper reviews those inverse electrocardiographic solutions that compute the electrical activity of the heart in terms of equivalent sources such as multipoles or multiple dipoles, as opposed to more realistic source formulations such as epicardial potentials. It treats, in succession, inverse solutions in terms of a single fixed-location dipole, a multipole series, moving dipoles, and, finally, multiple fixed-location dipoles. For each category of solution, simulation studies, animal experiments, and work involving human subjects are reviewed. Finally, more recent work that seeks to compute the cardiac activation isochrones, from the time integrals of the torso potentials during the QRS complex of the electrocardiogram, is described. The paper concludes with a discussion on the future of inverse electrocardiographic solutions in terms of equivalent sources.
Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations (2000)

Rubinstein-Taybi syndrome (RTS) is a malformation syndrome characterised by facial abnormalities, broad thumbs, broad big toes, and mental retardation. In a subset of RTS patients, microdeletions, translocations, and inversions involving chromosome band 16p13.3 can be detected. We have previously shown that disruption of the human CREB binding protein (CREBBP or CBP) gene, either by these gross chromosomal rearrangements or by point mutations, leads to RTS. CBP is a large nuclear protein involved in transcription regulation, chromatin remodelling, and the integration of several different signal transduction pathways. Here we report diagnostic analysis of CBP in 194 RTS patients, divided into several subsets. In one case the mother is also suspect of having RTS. Analyses of the entire CBP gene by the protein truncation test showed 4/37 truncating mutations. Two point mutations, one 11 bp deletion, and one mutation affecting the splicing of the second exon were detected by subsequent sequencing. Screening the CBP gene for larger deletions, by using different cosmid probes in FISH, showed 14/171 microdeletions. Using five cosmid probes that contain the entire gene, we found 8/89 microdeletions of which 4/8 were 5' or interstitial. This last subset of microdeletions would not have been detected using the commonly used 3' probe RT1, showing the necessity of using all five probes.
Oral Glucose Tolerance Test Minimal Model Indexes of β-Cell Function and Insulin Sensitivity (2001)

The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies-the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT300-22) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (phis [10(9) min(-1)] and phid [10(9)]) and the insulin sensitivity index (SI) (10(5) dl/kg per min per pmol/l) were estimated by using the minimal model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the minimal model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT300-11) is the test of choice because the indexes it provides (phis = 36 +/- 3 [means +/- SE]; phid = 710 +/- 111; SI = 10.2 +/- 2.4) show excellent correlation and are not statistically different from those of FSOGTT300-22 (phis = 33 +/- 3; phid = 715 +/- 120; SI = 10.1 +/- 2.3). In conclusion, OGTT300-11, interpreted with C-peptide and glucose minimal models, provides a quantitative description of beta-cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT.
Infrared microspectroscopic imaging maps the spatial distribution of exogenous molecules in skin (2003)

Infrared (IR) microscopic imaging is used, in a series of proof-of-principle experiments to map the spatial distribution of two penetration enhancers, dimethylsulphoxide (DMSO) and propylene glycol, in skin. The current instrumentation utilizes a 64 x 64 array of IR detectors imaged at the focal plane of an IR microscope, each collecting a complete mid-infrared spectrum of the skin section on each pass of the interferometer. The spatial area sampled by each element in the array is approximately 6.3 x 6.3 microm. Any spectral parameter (e.g., arising from lipid or protein vibrational modes of the endogenous tissue or the exogenous component) may be quantitatively analyzed across the entire array of 4096 spectra, thereby generating an IR spectroscopic image of that particular parameter throughout the sample. The images directly reveal the spatial heterogeneity of the protein and lipid distributions. In transverse slices of skin, the depth dependencies of the spatial distribution of triglyceride and protein have been monitored, and compared to those of the exogenous penetration enhancers. Images of both DMSO and propylene glycol suggest that each penetrates the skin to a depth of at least 1 mm (under our experimental protocols), and reveals a spatial distribution that is essentially coincident with the protein constituents of the skin. These results demonstrate that IR microscopic imaging has great potential for mechanistic studies of topical, dermal, and transdermal delivery.
Modular Total Synthesis of Lamellarin D (2005)

[Chemical reaction: see text] A modular total synthesis of lamellarin D, a marine alkaloid with potent cytotoxic as well as topoisomerase I inhibition properties, has been accomplished. A sequential and regioselective bromination/Suzuki cross-coupling procedure was applied for the introduction of aryl groups at positions 1 and 2 of scaffold 1. Microwave-assisted 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidation to yield pyrroloisoquinoline 15, followed by phenol group deprotection and subsequent lactonization, gave lamellarin D (18% in eight steps from 1).
The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells (2003)

Human plasminogen contains structural domains that are termed kringles. Proteolytic cleavage of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate endothelial cell proliferation. The receptor for kringles 1-3 or 4 has been identified as cell surface-associated ATP synthase; however, the receptor for K5 is not known. Sequence homology exists between the plasminogen activator streptokinase and the human voltage-dependent anion channel (VDAC); however, a functional relationship between these proteins has not been reported. A streptokinase binding site for K5 is located between residues Tyr252-Lys283, which is homologous to the primary sequence of VDAC residues Tyr224-Lys255. Antibodies against these sequences react with VDAC and detect this protein on the plasma membrane of human endothelial cells. K5 binds with high affinity (Kd of 28 nm) to endothelial cells, and binding is inhibited by these antibodies. Purified VDAC binds to K5 but only when reconstituted into liposomes. K5 also interferes with mechanisms controlling the regulation of intracellular Ca2+ via its interaction with VDAC. K5 binding to endothelial cells also induces a decrease in intracellular pH and hyperpolarization of the mitochondrial membrane. These studies suggest that VDAC is a receptor for K5.
The haemodynamics of human septic shock* (2001)

In the time it has taken medicine to develop the techniques to describe the circulatory changes of severe infections, both pattern and process have been profoundly influenced by the use of intravenous fluids, vasopressors, antibiotics, steroids, mechanical ventilation and haemoflltration. Constant features of severe sepsis include a reduction in peripheral vascular tone on both the arterial and venous sides of the circulation, a defect in oxygen utilisation resulting in lactic acidosis, and varying degrees of myocardial dysfunction. These events have a temporal progression, the precise pattern observed depending on the tempo of the infection, the influence of therapeutic manoeuvres, the age and comorbidities of the patient, and the time the observations are made in the course of events. Early sepsis is accompanied by a decrease in systemic vascular resistance and a metabolic acidosis. The clinical picture includes fever, tachycardia, tachypnoea, respiratory alkalosis and an increased cardiac output with warm, dry peripheries and a bounding pulse. Advanced sepsis involves varying degrees of venous and myocardial contractile failure, and is characterised by progressive acidaemia, respiratory failure and marked sympathetic adrenergic activation. In the absence of vigorous fluid resuscitation, the cardiac output is decreased and the patients are cold, clammy peripherally shut down, and frequently confused, obtunded or comatose. In infections with a silent primary focus (predominantly involving Gram-negative organisms), this stage is frequently the first to attract the attention of attending staff. Late sepsis is characterised by profound acidaemia, vascular hypo-responsiveness, multiple organ failure and death.