gebhart/patrepeval huggingface dataset:
Tomato Extract for Hypertension? (2009)

In this issue of Cardiovascular Drugs and Therapy, professor Paran and her colleagues report on the beneficial effect of tomato extract on blood pressure in patients who were insufficiently controlled with antihypertensive drugs [1]. In a randomized, placebo-controlled, double-blind cross-over trial they compared the extract to placebo in 50 hypertensive patients who had already been treated with a variety of drugs. While placebo did not have a measurable effect on blood pressure, the extract caused a fall of approximately 13/4 mmHg. The magnitude of this result is comparable to what the same investigators found earlier in a group of untreated subjects with mild hypertension [2]. Taken together, this suggests that the use of antihypertensive agents as in the current study did not modify the hypotensive potential of the extract. This makes the observations even more clinically meaningful and it certainly adds a new tool to the array of life-style interventions which we frequently recommend to our patients. A strong point in the study is that blood pressure was always measured with an automatic device. Nevertheless, it should also be noted that a substantial portion of the study population was over 65 years of age. As ageing is generally thought to be associated with increased oxidative stress, it may be that there is more to be gained with antioxidant therapy in the elderly than in the young. Whether the beneficial effects of tomato extract can be extrapolated to patients with less advanced age, thus remains to be determined. It would also be interesting to know whether a high baseline intake of antioxidant substances from whatever source would enhance or just mitigate the response to the extract. Although Paran and associates have carefully executed their study, there is a point of concern. In fact, the degree of blood pressure changes that they observed is greater than what one would expect. With a baseline blood pressure of, on average, 139/80 mmHg when the two groups were combined one would not anticipate a change in systolic pressure of 10 mmHg or more. Even the most powerful drugs usually do not produce that effect. One wonders, therefore, whether other factors could have contributed to the decline in pressure. Indeed, with other life-style measures such as a high intake of fruit and vegetables gave a fall in blood pressure of ‘only’ 4 mmHg systolic and 1.5 mmHg diastolic was observed [3]. Nevertheless, if at the population level the intake of tomatoes or tomato extract would increase to match that in the Paran study and if the population mean of blood pressure would fall to the same or perhaps a lesser extent, this would have enormous consequences in terms of reduction of cardiovascular risk. Despite the clear-cut effects of the tomato extract, it remains enigmatic why it lowers blood pressure so profoundly. Direct effects on blood pressure of lycopene, beta-carotene, folate, vitamin C and vitamin E have not been described. However, tomatoes are rich in potassium, Cardiovasc Drugs Ther (2009) 23:107–108 DOI 10.1007/s10557-008-6161-4
Pharmacotherapy of head and neck squamous cell carcinoma (2009)

Various single-agent and multi-agent chemotherapeutic regimens have been examined in the context of randomized clinical trials in locally advanced HNSCC for definitive, induction and adjuvant settings. Results from these clinical trials support the use of cisplatin-based chemoradiation as the standard of care for the definitive and adjuvant settings. Recent evidence indicates that cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is highly active as a single agent and in combination with standard chemotherapy and/or RT. Future studies should focus to determine the optimal pharmacotherapeutic regimens for use in locally advanced HNSCC.
The Rheumatoid Arthritis Shared Epitope Triggers Innate Immune Signaling via Cell Surface Calreticulin (2007)

The shared epitope (SE), carried by the vast majority of rheumatoid arthritis patients, is a 5-aa sequence motif in the third allelic hypervariable region of the HLA-DRbeta chain. We have recently demonstrated that the SE acts as an allele-specific ligand that triggers NO-mediated pro-oxidative signaling in opposite cells. The identity of the cell surface molecule that interacts with the SE is unknown. Using affinity chromatography purification, cell-binding assays, surface plasmon resonance, and time-resolved fluorescence resonance energy transfer techniques, we have identified cell surface calreticulin (CRT) as the SE-binding molecule. SE-triggered signaling could be blocked by anti-CRT Abs or Abs against CD91 and by CRT-specific antisense or small-interfering RNA oligonucleotides. Embryonic fibroblasts from crt(-/-) or CD91-deficient mice failed to transduce SE-triggered signals. Exogenously added soluble CRT attached to the cell surface and restored SE-triggered signaling responsiveness in crt(-/-) cells. These data indicate that cell surface CRT, a known innate immunity receptor, which has been previously proposed as a culprit in autoimmunity, plays a critical role in SE-triggered signal transduction.
De-Repression of PDGFRβ Transcription Promotes Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Glioblastoma Patients (2013)

These results provide the fi rst clinical and biologic evidence for receptor tyrosinekinase (RTK) "switching" as a mechanism of resistance to EGFR inhibitors in GBM and provide a molecular explanation of how tumors can become "addicted" to a non amplified, nonmutated, physiologically regulated RTK to evade targeted treatment.
Code bubbles (2010)

Developers spend significant time reading and navigating code fragments spread across multiple locations. The file-based nature of contemporary IDEs makes it prohibitively difficult to create and maintain a simultaneous view of such fragments. We propose a novel user interface metaphor for code understanding based on collections of lightweight, editable fragments called bubbles, which form concurrently visible working sets. We present the results of a qualitative usability evaluation, and the results of a quantitative study which indicates Code Bubbles significantly improved code understanding time, while reducing navigation interactions over a widely-used IDE, for two controlled tasks.
Prophylactic Anti-Infective Activity of Poly-[1-6]-β-d-Glucopyranosyl-[1-3]-β-d-Glucopyranose Glucan in a Guinea Pig Model of Staphylococcal Wound Infection (1998)

ABSTRACT The judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infections by stimulation of the host immune system. To test this hypothesis, we administered poly-[1-6]-β- d -glucopyranosyl-[1-3]-β- d -glucopyranose glucan (PGG glucan), which enhances neutrophil microbicidal activity, intravenously to guinea pigs in doses ranging from 0.015 to 4 mg/kg of body weight on the day before, on the day of, and on the day after intermuscular inoculation with methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis . Abscesses were identified at 72 h, and median infective doses (ID 50 ) and statistical significance were determined by logistic regression. Guinea pigs receiving PGG glucan and inoculated with methicillin-resistant S. aureus and S. epidermidis exhibited ID 50 of as much as 2.5- and 60-fold higher, respectively, than those of control guinea pigs not receiving PGG glucan. Maximal protection was observed with a dose of 1 mg of PGG glucan per kg, and efficacy was reduced at higher as well as at lower PGG glucan doses. Furthermore, a single dose of PGG glucan given 24 h following bacterial inoculation was found to be effective in preventing infection. We conclude that PGG glucan reduces the risk of staphylococcal abscess formation. Neutrophil-activating agents are a novel means of prophylaxis against surgical infection and may be less likely than antibiotics to be affected adversely by the increasing antibiotic resistance of nosocomial pathogens.
Threshold characteristics of planar and index-guided microcavity lasers (1995)

Lasing threshold modes are studied experimentally for microcavity lasers fabricated to operate either as planar cavities, in which the mode is established by the emitter distribution, or as index-guided modes in the planar cavity with weak three-dimensional confinement. For no lateral index guiding, the lasing mode area is suggested to depend on the gain saturation. For lateral index confinement to a small area, spectral and radiation pattern measurements show that the spontaneous emission coupling is increased, and reduces the lasing threshold even in the presence of an increased loss.
In Vivo Imaging of HIV Protease Activity in Amplicon Vector-transduced Gliomas (2004)

In vivo imaging of endogenously expressed mammalian proteases has been useful for the detection of cancer and preneoplastic lesions, for staging of inflammatory and autoimmune diseases, and for testing the efficacy of novel protease inhibitors. Here we report on the synthesis of a novel imaging probe that is specific for HIV-1 protease (PR). The probe was designed to be biocompatible, i.v. injectable, and detectable by fluorescence imaging. Human Gli36 glioblastoma cells infected with an human simplex virus amplicon vector expressing HIV-1PR showed specific fluorescence activation, an effect that could be inhibited by the HIV-1PR inhibitor, indinavir. The transfer of the HIV-1PR marker gene could be detected in vivo after intratumoral delivery of the human simplex virus-amplicon vector. These results are the first proof of principle that viral proteases can directly be imaged in vivo. These findings may be directly applicable in using viral protease expression as a transgene marker in tumor therapy and may have implications in testing the efficacy of HIV-1PR inhibitors in vivo.
Matrix Metalloproteinase-9 (MMP-9) Is Synthesized in Neurons of the Human Hippocampus and Is Capable of Degrading the Amyloid-β Peptide (1–40) (1996)

We reported earlier that the levels of Ca 2+ -dependent metalloproteinases are increased in Alzheimer’s disease (AD) specimens, relative to control specimens. Here we show that these enzymes are forms of the matrix metalloproteinase MMP-9 (EC 3.4.24.35 ) and are expressed in the human hippocampus. Affinity-purified antibodies to MMP-9 labeled pyramidal neurons, but not granular neurons or glial cells. MMP-9 mRNA is expressed in pyramidal neurons, as determined with digoxigenin-labeled MMP-9 riboprobes, and the presence of this mRNA is confirmed with reverse transcriptase PCR. The cellular distribution of MMP-9 is altered in AD because 76% of the total 100 kDa enzyme activity is found in the soluble fraction of control specimens, whereas only 51% is detectable in the same fraction from AD specimens. The accumulated 100 kDa enzyme from AD brain is latent and can be converted to an active form with aminophenylmercuric acetate. MMP-9 also is detected in close proximity to extracellular amyloid plaques. Because a major constituent of plaques is the 4 kDa β-amyloid peptide, synthetic Aβ 1–40 was incubated with activated MMP-9. The enzyme cleaves the peptide at several sites, predominantly at Leu 34 -Met 35 within the membrane-spanning domain. These results establish that neurons have the capacity to synthesize MMP-9, which, on activation, may degrade extracellular substrates such as β-amyloid. Because the latent form of MMP-9 accumulates in AD brain, it is hypothesized that the lack of enzyme activation contributes to the accumulation of insoluble β-amyloid peptides in plaques.
Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study (2006)

Bcl-6 protein expression, a marker of germinal center origin, has been associated with a favorable prognosis in diffuse large B-cell lymphoma (DLBCL). To determine the prognostic significance of this marker when rituximab (R) was added to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, we prospectively studied Bcl-6 protein expression by immunohistochemical staining of 199 paraffin-embedded specimens from patients enrolled in the US Intergroup phase 3 trial comparing R-CHOP to CHOP with or without maintenance R. In Bcl-6(-) patients, failure-free survival (FFS) and overall survival (OS) were prolonged for those treated with R-CHOP alone compared to CHOP alone (2-year FFS 76% versus 9%, P < .001; 2-year OS 79% versus 17%, P < .001). In contrast, no differences in FFS and OS were detected between treatment arms for Bcl-6(+) cases. In the multivariate analysis, treatment arm (CHOP versus R-CHOP) was the major determinant of both FFS (P < .001) and OS (P < .001) for the Bcl-6(-) subset, whereas the International Prognostic Index risk group was the only significant predictor of outcome among Bcl-6(+) cases. Bcl-2 protein expression was not predictive of outcome in either group. In this study, we observed a reduction in treatment failures and death with the addition of R to CHOP in Bcl-6(-) DLBCL cases only. Our finding that Bcl-6(+) cases did not benefit from the addition of R to CHOP requires independent confirmation.
Correction of motion artifact in transmembrane voltage-sensitive fluorescent dye emission in hearts (2004)

Fast voltage-sensitive dyes are widely used to image cardiac electrical activity. Typically, the emission spectrum of these fluorochromes is wavelength shifted with altered membrane potential, but the optical signals obtained also decay with time and are affected by contraction. Ratiometry reduces, but may not fully remove, these artifacts. An alternate approach has been developed in which the time decay in simultaneously acquired short- and long-wavelength signals is characterized nonparametrically and removed. Motion artifact is then identified as the time-varying signal component common to both decay-corrected signals and subtracted. Performance of this subtraction technique was compared with ratiometry for intramural optical signals acquired with a fiber-optic probe in an isolated, Langendorff-perfused pig heart preparation (n = 4) stained with di-4-ANEPPS. Perfusate concentration of 2,3-butanedione monoxime was adjusted (7.5-12.5 mM) to alter contractile activity. Short-wavelength (520-600 nm) and long-wavelength (>600 nm) signals were recorded over 8-16 cardiac cycles at 6 sites across the left ventricular free wall in sinus rhythm and during pacing. A total of 451 such data sets were acquired. Appreciable wall motion was observed in 225 cases, with motion artifact classed as moderate (less than modulation due to action potential) in 187 and substantial (more than modulation due to action potential) in 38. In all cases, subtraction performed as well as, or better than, ratiometry in removing motion artifact and decay. Action potential morphology was recovered more faithfully by subtraction than by ratiometry in 58 of 187 and 31 of 38 cases with moderate and substantial motion artifact, respectively. This novel subtraction approach may therefore provide a means of reducing the concentration of uncoupling agents used in cardiac optical mapping studies.
Three-dimensional micromachined on-chip inductors for high frequency applications (2002)

Demands for wireless communication are ever-escalating for consumer and military communication applications. The requirements of portability, more functionality and lower cost have been driving forces toward smaller, more sophisticated and flexible wireless devices with lower power consumption. To meet these requirements, monolithically integrated passive inductors with high Q-factors and high self-resonant frequencies are desirable. Q-factor and self-resonant frequency of an inductor are significantly degraded at high frequencies due to conductor ohmic loss, magnetically induced eddy current in the conductive substrate, and lower self-resonant frequency from capacitance between conductive substrate and conductors. In this dissertation, novel three-dimensional arch-like solenoid and dome-shaped spiral inductors are designed, fabricated, and characterized. MEMS-based fabrication techniques such as copper electroplating through voids in thick SU-8 photoresist molds and EAGLE2100 conformal photoresist molds on sacrificial arch-like or dome-shape SJR5740 photoresist mounds are utilized. An air gap between the inductor and the silicon substrate is used to reduce the degradations of inductor performance. According to the Sonnet electromagnetic simulations, 30 μm air-gap suspension over the substrate is an adequate choice for these inductors. Suspended arch-like solenoid copper inductor has flat bottom conductor connected to arch-like top conductor with an air core in between. This design has only 2 contact points per inductor turn to minimize series resistance. Suspended domeshaped spiral copper inductor is fabricated on a sacrificial photoresist dome with the outer end connected to one probe pad, and the inner end connected to the other probe pad through vias and an air-bridge. The sidewalls of spiral turns in this design overlap less with each other thereby reducing inter-turn capacitances. Fabricated inductors are characterized and modeled at high frequencies from Sparameter measurements. ABCD-parameters, derived from the S-parameters are translated into a simplified physical π-model. The resulting arch-like suspended inductors with 2-5 turns have inductances between 0.62 to 0.79 nH, peak Q-factor values between 15.42 to 17 at peak-Q frequencies between 4.7 GHz to 7.0 GHz, and self-resonant frequencies between 47.6 GHz to 88.6 GHz. The 3-turn dome-shaped spiral inductor has inductance of 3.37 nH, peak Q-factor of 35.9 at 1.65 GHz, and self-resonant frequency at 18.74 GHz.
Tongue-muscle Training by Intraoral Electrical Neurostimulation in Patients with Obstructive Sleep Apnea (2004)

Although tongue-muscle training cannot generally be recommended for the treatment of sleep apnea, the method has proven to be effective in the treatment of snoring.
Analysis of Fetal Blood Cells in the Maternal Circulation: Challenges, Ongoing Efforts, and Potential Solutions (2004)

The invasive procedures amniocentesis and chorionic villus sampling (CVS) are routinely applied in pregnancies at risk for fetal abnormalities and the results obtained are the gold standard for prenatal diagnosis. Because these methods of fetal cell procurement involve a 0.5-2% risk for fetal loss, they are recommended mainly in cases at high risk for fetal genetic or cytogenetic abnormalities. The development of a reproducible, reliable, noninvasive method based on retrieval of rare fetal cells from the maternal circulation will render testing feasible for the general population. Despite intensive investigation, a satisfactory, clinically acceptable method has not yet emerged. Several cell types have been targeted to this end, mostly nucleated red blood cells (NRBC), CD34+ hematopoietic progenitors, and trophoblasts. Although these cell types have been unequivocally proven to be present in the maternal circulation, each bears a significant disadvantage, rendering their application in clinical testing currently impossible: NRBC cannot be expanded in culture, thereby ruling out metaphase chromosome analysis, an essential component of prenatal diagnosis. CD34+ cells do posses the potential for in vitro proliferation, however, they have been found to persist in the maternal circulation after delivery, thereby complicating diagnosis in consecutive pregnancies. Trophoblasts are not consistently detected in the maternal circulation. Moreover, due to the lack of a definitive fetal cell marker and a reliable sorting method, foolproof fetal cell identification of any of these cell types is not possible. This report outlines the obstacles that impede development of a method for noninvasive fetal cell sampling for prenatal genetic diagnosis, along with a description of our efforts to analyze simultaneously two fetal blood cell types, NRBC and CD34+ cells in maternal blood during pregnancy, and the problems encountered. This work and that of others lead us to suggest potential future directions to help develop this important technique.
Thalidomide Therapy (1985)

In an open trial, 35 patients suffering from a variety of dermatologic conditions were treated with thalidomide. The drug was shown to be a valuable addition to the therapeutic armamentarium; however, the occurrence of a peripheral neuropathy will limit its use just as its teratogenic side effects have done for many years.
Synthesis of the New Chiral Aminodiphosphine Ligands (R)- and (S)-(.alpha.-Methylbenzyl)bis(2-(diphenylphosphino)ethyl)amine and Their Use in the Enantioselective Reduction of .alpha.,.beta.-Unsaturated Ketones to Allylic Alcohols by Iridium Catalysis (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of the New Chiral Aminodiphosphine Ligands (R)- and (S)-(.alpha.-Methylbenzyl)bis(2-(diphenylphosphino)ethyl)amine and Their Use in the Enantioselective Reduction of .alpha.,.beta.-Unsaturated Ketones to Allylic Alcohols by Iridium CatalysisClaudio Bianchini, Erica Farnetti, Lionel Glendenning, Mauro Graziani, Giorgio Nardin, Maurizio Peruzzini, Eliana Rocchini, and Fabrizio ZanobiniCite this: Organometallics 1995, 14, 3, 1489–1502Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/om00003a059https://doi.org/10.1021/om00003a059research-articleACS PublicationsRequest reuse permissionsArticle Views689Altmetric-Citations50LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts