gebhart/patrepeval huggingface dataset:
Age-Dependent Cognitive Deficits and Neuronal Apoptosis in Cyclooxygenase-2 Transgenic Mice (2001)

The cyclooxygenases catalyze the rate-limiting step in the formation of prostaglandins from arachidonic acid and are the pharmacological targets of (NSAIDs). In brain, cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, is selectively expressed in neurons of the cerebral cortex, hippocampus, and amygdala. As an immediate-early gene, COX-2 is dramatically and transiently induced in these neurons in response to NMDA receptor activation. In models of acute excitotoxic neuronal injury, elevated and sustained levels of COX-2 have been shown to promote neuronal apoptosis, indicating that upregulated COX-2 activity is injurious to neurons. COX-2 may also contribute to the development of Alzheimer's disease, for which early administration of NSAIDs is protective against development of the disease. To test the effect of constitutively elevated neuronal COX-2, transgenic mice were generated that overexpressed COX-2 in neurons and produced elevated levels of prostaglandins in brain. In cross-sectional behavioral studies, COX-2 transgenic mice developed an age-dependent deficit in spatial memory at 12 and 20 months but not at 7 months and a deficit in aversive behavior at 20 months of age. These behavioral changes were associated with a parallel age-dependent increase in neuronal apoptosis occurring at 14 and 22 months but not at 8 months of age and astrocytic activation at 24 months of age. These findings suggest that neuronal COX-2 may contribute to the pathophysiology of age-related diseases such as Alzheimer's disease by promoting memory dysfunction, neuronal apoptosis, and astrocytic activation in an age-dependent manner.
Alimentação de porcas gestantes e lactantes com dietas contendo saponinas (2006)

Foi realizado um experimento para avaliar o desempenho de porcas e suas leitegadas alimentadas com dietas que continham saponinas. Trinta porcas geneticamente homogêneas foram distribuídas em dois tratamentos, dieta testemunha e dieta testemunha com adição de 160ppm de fontes de saponinas. O delineamento utilizado foi o de blocos ao acaso, tendo como fator de bloqueamento a ordem de parto. Nas porcas, foram avaliados: o consumo de ração, características das fezes (cor e textura) e escore corporal. Nos leitões, foram avaliados: número de nascidos vivos, nascidos mortos, mumificados; pesos ao nascer e ao desmame e mortalidade na lactação. Não foram encontradas diferenças na cor das fezes das fêmeas. Na textura, as fezes das fêmeas que receberam a dieta com a adição de saponinas foram cerca de 11% mais duras (P&lt;0,05). Na última semana de lactação, as fêmeas alimentadas com a adição de saponinas apresentaram um escore corporal 12% superior (P&lt;0,05) às fêmeas controle. Não foram encontradas diferenças (P&gt;0,05) nos leitões em relação as variáveis nascidos vivos, nascidos mortos e mumificados. Os leitões das fêmeas que receberam dietas contendo saponinas foram mais pesados (P&lt;0,05) ao nascer (1,2 x 1,4kg) e ao desmame (5,5x 5,9kg). Porcas alimentadas nos últimos 10 dias de gestação e na lactação com dietas contendo 160ppm de saponinas têm melhor escore corporal no final da lactação e suas leitegadas são mais pesadas ao nascer e ao desmame.
The anti-CD20 antibody rituximab reduces the Th17 cell response (2011)

Rituximab reduced the local Th17 response in RA patients, whereas it did not influence Th1 cell, Treg cell, or TNFα responses. The decreased Th17 response was associated with reduced inflammation and better clinical outcome. Moreover, inhibition of the Th17 response by rituximab was lost in the absence of B cells, providing evidence that the effects of rituximab are due to B cell depletion. These data demonstrate an unexpected role of B cells in the development of Th17 responses, which could possibly lead to B cell-based strategies for the treatment of Th17-related autoimmune diseases.
Quantitative studies of autonomic function (2005)

Dysfunction of the peripheral and central autonomic nervous system is common in many neurological and general medical diseases. The quantitative assessment of sympathetic and parasympathetic function is essential to confirm the diagnosis of autonomic failure, to provide the basis for follow-up examinations, and potentially to monitor successful treatment. Various procedures have been described as useful tools to quantify autonomic dysfunction. The most important tests evaluate cardiovascular and sudomotor autonomic function. In this review, we therefore focus on standard tests of cardiovascular and sudomotor function such as heart-rate variability at rest and during deep breathing, active standing, and the Valsalva maneuver, and on the sympathetic skin response. These tests are widely used for routine clinical evaluation in patients with peripheral neuropathies. Refined methods of studying heart-rate variability, baroreflex testing, and detailed measures of sweat output are mostly used for research purposes. In this context, we describe the spectral analysis of slow modulation of heart rate or blood pressure, reflecting sympathetic and parasympathetic influences, and consider various approaches to baroreflex testing, the thermoregulatory sweat test, and the quantitative sudomotor axon reflex test. Finally, we discuss microneurography as a technique of direct recording of muscle sympathetic nerve activity.
Sterols. I. A Study of the 22-Ketosteroids1 (1945)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSterols. I. A Study of the 22-Ketosteroids1Wayne Cole and Percy L. JulianCite this: J. Am. Chem. Soc. 1945, 67, 8, 1369–1375Publication Date (Print):August 1, 1945Publication History Published online1 May 2002Published inissue 1 August 1945https://pubs.acs.org/doi/10.1021/ja01224a044https://doi.org/10.1021/ja01224a044research-articleACS PublicationsRequest reuse permissionsArticle Views175Altmetric-Citations34LEARN 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
Managing the teratogenic risk of thalidomide and lenalidomide: an industry perspective (2010)

Celgene has developed and operated pregnancy prevention programs since 1998 with the first approval of thalidomide in the US. With the development and marketing of lenalidomide, an analog of thalidomide, the company further advanced its risk management activities, which now cover several territories across the globe. To date, the program is a success in as much as it has minimized the risk of fetal exposure and subsequent development of fetal malformations. Nonetheless, the company understands the need to provide a mechanism for intervention and remediation when at-risk behaviors are identified, and this forms an integral part of the risk management processes. The implementation of the thalidomide and lenalidomide pregnancy prevention program partners patients, healthcare professionals, regulators and the company in a spirit of shared responsibility. This paper also presents the authors' experience and perspective on the challenges of managing a pregnancy prevention program, which at its core aims at ensuring that the product's benefits outweigh the risk of fetal exposure.
D‐4F, An Apolipoprotein A‐I Mimetic Peptide, Prevents Endothelial Dysfunction Induced By Myeloperoxidase‐Derived Hypochlorous Acid (2007)

Myeloperoxidase (MPO) and its principal product hypochlorous acid (HOCl) are pro‐atherogenic molecules that functionally modify LDL and HDL and impair endothelium‐dependent relaxation. MPO‐ and HOCl‐induced changes in HDL function are thought to occur via modifications at the level of apo A‐I. In the current study, we tested the hypothesis that the apo A‐I mimetic peptide D‐4F prevents HOCl‐induced endothelial dysfunction by acting as a reactive substrate for HOCl. Rat aortic ring segments were isolated and suspended in an isolated tissue bath. Exposure of tissues to HOCl (10 μM, 30 min) resulted in a 51% inhibition of acetylcholine (Ach)‐induced relaxation compared to saline‐treated controls. Concurrent treatment with HOCl and D‐4F (10 μM) significantly improved the response to Ach (15% inhibition vs control). Biochemical analyses revealed a rapid and significant reduction in the tryptophan fluorescence of D‐4F, when mixed with HOCl at a 1:1 molar ratio. Mass spectral analysis of this reaction product confirmed oxidation of the sole tryptophan residue in the peptide. While D‐4F was previously shown to inhibit lesion formation and inflammation in experimental models of atherosclerosis, results of the current studies suggest that oxidant scavenging may represent an additional anti‐atherogenic mechanism of D‐4F action. Supported by NIH DK070040 and the UAB Cancer Center Mass Spectrometry Shared Facility.
Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants (2016)

Amygdala circuitry and early life stress (ELS) are both strongly and independently implicated in the neurobiology of depression. Importantly, animal models have revealed that the contribution of ELS to the development and maintenance of depression is likely a consequence of structural and physiological changes in amygdala circuitry in response to stress hormones. Despite these mechanistic foundations, amygdala engagement and ELS have not been investigated as biobehavioral targets for predicting functional remission in translational human studies of depression. Addressing this question, we integrated human neuroimaging and measurement of ELS within a controlled trial of antidepressant outcomes. Here we demonstrate that the interaction between amygdala activation engaged by emotional stimuli and ELS predicts functional remission on antidepressants with a greater than 80% cross-validated accuracy. Our model suggests that in depressed people with high ELS, the likelihood of remission is highest with greater amygdala reactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, remission is associated with lower amygdala reactivity to both rewarding and threat-related stimuli. This full model predicted functional remission over and above the contribution of demographics, symptom severity, ELS, and amygdala reactivity alone. These findings identify a human target for elucidating the mechanisms of antidepressant functional remission and offer a target for developing novel therapeutics. The results also offer a proof-of-concept for using neuroimaging as a target for guiding neuroscience-informed intervention decisions at the level of the individual person.
A suspended-membrane balanced frequency doubler to 200 GHz (2006)

A 200 GHz fixed tuned balanced frequency doubler using suspended membrane technology and integrated diodes is described. The design is discussed with reference to DC and RF circuit losses, integrated diode-membrane structure and ease of construction. Finite element analysis and harmonic balance methods were used to optimise multiplier performance. Predictions show peak power output of 15 mW and peak efficiency of 12% at 200 GHz. Key device fabrication steps are also described.
Simultaneous treatment of concurrent rejection and tissue invasive cytomegalovirus disease without detrimental effects upon patient or allograft survival (1992)

Posttransplant cytomegalovirus (CMV) infection has been directly and temporally correlated with decreased patient and allograft survival. Because of this association, prior dogma has dictated that immunosuppression be decreased or maintained, but not increased, and thus rejection episodes have not been treated during active CMV infection. Since 1987, we have treated a group of patients who developed concurrent (within 1–3 days) mild to moderate acute rejection and mild to moderate tissue invasive CMV disease (TI‐CMV) with antirejection and antiviral therapy simultaneously. 619 patients underwent renal transplantation between 5/7/87 and 12/13/90 [535 kidney (253 living related, 282 cadaver) and 84 kidney‐pancreas]. 18 patients presented with concurrent evidence of TI‐CMV plus acute kidney or pancreas allograft rejection. Treatment consisted of iv ganciclovir (DHPG, 5 mg/kg iv q 12 h, mean = 14.4 days) for TI‐CMV and initial oral or iv steroids (followed by ALG or OKT3 in 13 patients) for rejection. At 30 days, all 18 patients with concurrent TI‐CMV and rejection were successfully treated for CMV without DHPG toxicity, although 2 allografts were lost due to unrelenting rejection requiring nephrectomy. 4 patients developed recurrent TI‐CMV and 1 patient developed recurrent rejection &gt;30 days after simultaneous therapy, all of which were successfully treated. A total of 4 deaths occurred due to the following causes: pulmonary embolus, cerebrovascular accident. Candida sepsis, and Aspergillus sepsis, the latter subsequent to treatment of recurrent rejection. We analyzed outcome in patients who developed TI‐CMV post‐rejection (&gt; 14 days) or TI‐CMV without rejection and who received DHPG. and noted that patient and allograft survival was not statistically different compared to patients who received simultaneous therapy for both disease processes (p&gt;0.05). Recipients with or without rejection who never developed TI‐CMV. however, did exhibit increased patient and allograft survival when compared to those who were treated for TI‐CMV alone or simultaneous TI‐CMV plus rejection (p&lt;0.01). Based upon this analysis, we concluded that: 1) simultaneous treatment of concurrent TI‐CMV and acute rejection is feasible, and 2) this docs not magnify the adverse effects related to TI‐CMV alone, and recommended that: 1) antirejection therapy be instituted with simultaneous administration of DHPG in patient with proven rejection and suspected TI‐CMV. 2) the diagnostic work‐up for CMV and other pathogens should be vigorously pursued in this setting, and 3) if evidence of progression of CMV disease occurs (despite absence of this event in this series) that antirejection therapy be withdrawn.
A Novel Nucleoside Prodrug-Activating Enzyme:  Substrate Specificity of Biphenyl Hydrolase-like Protein (2004)

Biphenyl hydrolase-like protein (BPHL, NCBI accession number NP_004323) is a novel human serine hydrolase recently identified as a human valacyclovirase, catalyzing the hydrolytic activation of the antiviral prodrugs valacyclovir and valganciclovir. The substrate specificity of BPHL was investigated with a series of amino acid ester prodrugs of the therapeutic nucleoside analogues: acyclovir, zidovudine, floxuridine, 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl) benzimidazole, and gemcitabine. The hydrolysis of typical esterase and aminopeptidase substrates by BPHL was also investigated. The results indicate that the substrate specificity of BPHL is largely determined by the amino acid acyl promoiety, and is less sensitive to the nucleoside parent drugs. For all nucleoside parent drugs, BPHL preferred the hydrophobic amino acids valine, phenylalanine, and proline over the charged amino acids lysine and aspartic acid. The position and monoester or diester form of the prodrug were also important, with BPHL exhibiting higher affinity for the 5'-esters than for the 3'-esters and the 3',5'-diesters irrespective of amino acid type. Further, the presence of the 3'-amino acid ester considerably reduced the hydrolysis rate of the 5'-amino acid ester functionality. BPHL exhibited stereoselectivity with an L/D specificity ratio of 32 for 5'-valyl floxuridine and 1.5 for 5'-phenylalanyl floxuridine. The substrate specificity suggests that the substrate-binding pocket of BPHL has a hydrophobic acyl binding site which can accommodate the positively charged alpha-amino group, while having an alcohol leaving group binding site that can accommodate nucleoside analogues with a relatively generous spatial allowance. In conclusion, BPHL catalyzes the hydrolytic activation of amino acid esters of a broad range of therapeutic nucleoside analogues in addition to valacyclovir and valganciclovir and has considerable potential for utilization as an activation target for design of antiviral and anticancer nucleoside analogue prodrugs.
Augmentation of tumor targeting in a line of glioma-specific mouse cytotoxic T-lymphocytes by retroviral expression of mouse gamma-interferon complementary DNA. (1988)

As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse gamma-interferon (IFN-gamma) into a specific cytotoxic T-lymphocyte clone, designated E-4, against 203 glioma cells (a 20-methylcholanthrene-induced mouse glioma line) and confirmed the efficacy of IFN-gamma production from the exogenous gene on augmentation of tumor targeting. Of five, two gene-transferred subclones constitutively produced 8 to 10 times the amount of IFN-gamma as compared with the parental E-4. Correspondingly, these two subclones exhibited 2 to 3 times higher killing activity against 203 glioma than the parental cells; the enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+,3+, and asialo-GM1-. The surface expression of a major histocompatibility complex Class I antigen, H-2Kb, was not altered remarkably, but the Class II antigen, I-Ab, was partially and slightly enhanced on the two IFN-gamma-producing sublines mentioned above on fluorescence-activated cell sorter analysis. Since it is considered that in the vicinity of the constitutively IFN-gamma producing cytotoxic T-lymphocyte cells tumor cells are exposed to a high concentration of IFN-gamma, the cells may be stimulated to induce or enhance the expression of surface antigens including major histocompatibility complex antigens as well as tumor-associated antigens relevant to immune recognition. The 203 glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. Taken together, the results suggested that the augmented specific tumor-killing activity of our gene-transferred cytotoxic T-lymphocytes was ascribed to the constitutive production of IFN-gamma derived from the exogenous gene.
The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila (2004)

Diverse extrinsic and intrinsic cues must be integrated within a developing organism to ensure appropriate growth at the cellular and organismal level. In Drosophila, the insulin receptor/TOR/S6K signaling network plays a fundamental role in the control of metabolism and cell growth. Here we show that scylla and charybdis, two homologous genes identified as growth suppressors in an EP (enhancer/promoter) overexpression screen, act as negative regulators of growth. The simultaneous loss of both genes generates flies that are more susceptible to reduced oxygen concentrations (hypoxia) and that show mild overgrowth phenotypes. Conversely, scylla or charybdis overactivation reduces growth. Growth inhibition is associated with a reduction in S6K but not PKB/Akt activity. Together, genetic and biochemical analysis places Scylla/Charybdis downstream of PKB and upstream of TSC. Furthermore, we show that scylla and charybdis are induced under hypoxic conditions and that scylla is a target of Drosophila HIF-1 (hypoxia-inducible factor-1) like its mammalian counterpart RTP801/REDD1, thus establishing a potential cross-talk between growth and oxygen sensing.
Application of 2-nitroso-1-naphthol-4-sulphonic acid for separation and preconcentration of trace cadmium and determination by differential pulse polarography (2005)

A highly selective, sensitive, rapid and economical differential pulse polarographic method has been developed for the determination of trace amount of cadmium in various standard alloys and biological samples after adsorption of its 2-nitroso-1-naphthol-4-sulphonic acid - tetradecyldimethylbenzylammonium chloride on microcrystalline naphthalene in the pH range of 5.7-11.0. After filtration, the solid mass is shaken with 9.0 mL of 1 M hydrochloric acid and cadmium is determined by differential pulse polarography (DPP). Cadmium can alternatively be adsorbed on 2-nitroso-1-naphthol-4-sulphonic acid-tetradecyldimethylbenzylammonium-naphthalene adsorbent packed in a column and determined. In this case, 0.9 μg of cadmium can be concentrated in a column from 300 mL of aqueous sample, where its concentration is as low as 3 ng/mL. Characterization of the electroactive process included an examination of the degree of reversibility. Various parameters such as the effect of pH, volume of aqueous phase, HCI concentration, reagent concentration, naphthalene concentration, shaking time and interference of a number of metal ions on the determination of cadmium have been studied in detail to optimize the conditions for determination in standard alloys and standard biological samples.
Structure and Order of Phosphonic Acid-Based Self-Assembled Monolayers on Si(100) (2010)

Organophosphonic acid self-assembled monolayers (SAMs) on oxide surfaces have recently seen increased use in electrical and biological sensor applications. The reliability and reproducibility of these sensors require good molecular organization in these SAMs. In this regard, packing, order, and alignment in the SAMs is important, as it influences the electron transport measurements. In this study, we examine the order of hydroxyl- and methyl-terminated phosphonate films deposited onto silicon oxide surfaces by the tethering by aggregation and growth method using complementary, state-of-art surface characterization tools. Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and in situ sum frequency generation (SFG) spectroscopy are used to study the order of the phosphonate SAMs in vacuum and under aqueous conditions, respectively. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry results show that these samples form chemically intact monolayer phosphonate films. NEXAFS and SFG spectroscopy showed that molecular order exists in the octadecylphosphonic acid and 11-hydroxyundecylphosphonic acid SAMs. The chain tilt angles in these SAMs were approximately 37° and 45°, respectively.