gebhart/patrepeval huggingface dataset:
Phase II trial of the anti-prostate specific membrane antigen (PSMA) monoclonal antibody (mAb) J591 plus low-dose interleukin-2 (IL-2) in patients (pts) with recurrent prostate cancer (PC) (2007)

15558 Background: The de-immunized mAb J591 recognizes the extracellular domain of PSMA and was engineered to induce antibody-dependent cellular cytotoxicity (ADCC). Low-dose IL-2 results in the clonal expansion of NK cells and may enhance ADCC. We conducted a phase 2 trial to determine the efficacy and toxicity of mAb J591 plus low-dose subcutaneous (SC) IL-2 in pts with recurrent PC. Methods: 17 pts with recurrent PC (2 groups: 11 with PSA relapse only; and 6 with progressive castrate metastatic disease) received continuous low-dose SC IL-2 (1.2 x 10 6 IU/m2/day) daily for 8 weeks with mAb J591 (25 mg/m 2 IV) weekly on weeks 4, 5 and 6 (1 cycle). Pts could receive a maximum of 3 cycles. Results: 16 evaluable pts received up to 3 cycles of therapy (16 pts, one cycle, 9 two cycles and 2 three cycles). Toxicity was mild and limited to fatigue and injection site reactions. At the end of cycle 1, PSA was stable (-50%&lt;change in PSA&lt;25%) in 9 of 16 patients, with PSA declines up to 34%. No PSA decline &gt;50% was observed. A post-hoc analysis of PSA kinetics showed 5 patients had a reduction in their PSA slope of =25%; 8 of the remaining 11 patients demonstrated PSA stabilization (- 25%&lt;change in PSA slope&lt;25%). PSA response was most commonly observed during weeks 4–6 of the cycle correlating with mAb administration. Flow cytometric analysis of peripheral blood mononuclear cells revealed an average increase in absolute NK cell count of 107% at week 4 and 117% at the end of cycle 1. Conclusions: The combination of mAb J591 with low-dose IL-2 was well tolerated and inhibited PSA kinetics in some patients, however no responses were seen. Repetitive dosed mAb J591 is a viable strategy for use in combination with immune modulatory or other therapies in recurrent prostate cancer. No significant financial relationships to disclose.
Generation of functional hepatocytes from mouse induced pluripotent stem cells (2009)

Induced pluripotent stem cells are derived from somatic cells by forced expression of several transcriptional factors. Induced pluripotent stem cells resemble embryonic stem cells in many aspects, such as the expression of certain stem cell markers, chromatin methylation patterns, embryoid body formation and teratoma formation. Therefore, induced pluripotent stem cells provide a powerful tool for study of developmental biology and unlimited resources for transplantation therapy. Here we reported the successful induction of mouse induced pluripotent stem cells and a simple and efficient process for generation of functional hepatocytes from mouse induced pluripotent stem cells by sequential addition of inducing factors. These induced pluripotent stem cell-derived hepatocytes, just as mouse embryonic stem cell-derived hepatocytes, expressed hepatic lineage markers including CK7, CK8, CK18, CK19, alpha-fetoprotein, albumin, Cyp7a1, and exhibited functional hepatic characteristics, including glycogen storage, indocyanine green (ICG) uptake and release, low-density lipoprotein (LDL) uptake and urea secretion. Although we observed some variations in the efficiency of hepatic differentiation between induced pluripotent stem cells and common mouse embryonic stem cell lines, our results indicate that mouse induced pluripotent stem cells can efficiently differentiate into functional hepatocytes in vitro, which may be helpful for the study of liver development and regenerative medicine.
Elimination of early Salmonella enteritidis infection after treatment with competitive-exclusion culture and enrofloxacin in experimentally infected chicks (2000)

The effect of normal avian gut flora (NAGF) and enrofloxacin administration on the early infection of young chicks by Salmonella enteritidis (SE) was determined using day-old White Leghorn chicks. Day- old chicks were divided into two groups, untreated control and NAGF-treated, and then infected with 10(6) cfu of SE per chick by oral gavage. The untreated, infected chicks were further divided into two groups and were either left untreated or medicated with a regimen of 10 mg/kg of enrofloxacin in drinking water daily for 10 d, followed by two doses of NAGF beginning at 10 and 8 wk of age in Trial 1 and Trial 2, respectively. Liver, spleen, and cecum samples were tested for the presence of SE, and immunological responsiveness was investigated up to 12 wk of age. Compared with the untreated group, the cecal colonization of SE was significantly (P < 0.05) decreased in the NAGF-treated group in Trials 1 and 2. No significant differences in organ infection were observed in the NAGF-treated vs. untreated birds. Although a significant effect of the combined treatment of enrofloxacin treatment and NAGF on the early infection was not shown in Trial 1, compared with enrofloxacin only or the untreated group, a significant reduction (P < 0.05) in the number of infected chickens and in the number of SE in the cecal contents was observed at 10 wk of age in Trial 2. The enrofloxacin treatment did not increase opportunistic colonization by SE due to the use of the antibiotic in either trial. The plasma and intestinal immunological responses were not significant at the early age (up to 12 wk) of the birds. The use of enrofloxacin, followed by NAGF, could aid the elimination of SE from young chicks persistently infected at an early age. The combined treatment, compared with enrofloxacin alone, protected chickens from reinfection by 40%.
The Role of Endothelin‐1 in Epidermal Hyperpigmentation and Signaling Mechanisms of Mitogenesis and Melanogenesis (1997)

The paracrine linkage of endothelins (ET) between keratinocytes and melanocytes suggested that ETs are intrinsic mediators for human melanocytes in UVB-induced pigmentation. In this study, the role of ET-1 in the epidermal hyperpigmentation was investigated in vivo and in vitro. The addition of 10 nM ET-1 induced a H-7 (10 microM) suppressible-increase in tyrosinase activity in cultured human melanocytes and was accompanied by elevated levels of tyrosinase and tyrosinase-related protein-1 mRNA expression as shown by Northern blotting. Analysis of signaling mechanisms leading to tyrosinase activation demonstrated the involvements of quick translocation of PKC, the H-7 (10 microM) suppressible-phosphorylation of the threonine residue of several proteins, and highly elevated level of cyclic AMP (4-fold over control). Reverse transcription polymerase chain reaction (RT-PCR) of RNA isolated from the epidermis of human skin exposed to UVB revealed that UVB irradiation with a dose of 2 MED caused a significant increase in the expressions of ET-1, IL-1 alpha, and tyrosinase mRNA signals 5 days after irradiation. The involvement of ET-1 in UVB-pigmentation was also corroborated by the experiments that the extracts of M. Chamomilla, which can act as an antagonist for ET-receptor binding-mediated signaling but has no inhibitory effect on tyrosinase activity in culture, had a significant inhibitory effect on UVB-induced pigmentation in vivo when daily applied immediately after UVB exposure to human skin. These findings suggest that ET-1 is an important mediator in the epidermis for UVB-induced pigmentation in vivo.
Design and synthesis of peptide inhibitors of blood coagulations. (1982)

Inhibition of blood coagulation by peptide aldehydes has been studied. Amino acid sequences were assembled from the P1-P2 portion of the cleavage sites(s) of clotting factors and residues selected experimentally. The thrombin-fibrinogen reaction could effectively be inhibited by D-Phe-Pro-Arg-H (GYKI-14,166) and Boc-D-Phe-Pro-Arg-H (GYKI-14,451). Plasmin digestion of fibrin could be retarded by Boc-Gln-Phe-Lys-H (GYKI-14,605) derived from a susceptible fragment, i.e. Asn-Phe-Lys decreases to Ser. However, such peptides could not retard the zymogen activations proceeding in Ca++ complexes (which seemed to be uneffected by heparin-antithrombin III, too). Inhibition of enzymes by peptide aldehydes showed marked substrate dependence.
Hydrogel-Based Protein Microchips: Manufacturing, Properties, and Applications (2003)

Here a simple, reproducible, and versatile method is described for manufacturing protein and ligand chips. The photo-induced copolymerization of acrylamide-based gel monomers with different probes (oligonucleotides, DNA, proteins, and low-molecular ligands) modified by the introduction of methacrylic groups takes place in drops on a glass or silicone surface. All probes are uniformly and chemically fixed with a high yield within the whole volume of hydrogel semispherical chip elements that are chemically attached to the surface. Purified enzymes, antibodies, antigens, and other proteins, as well as complex protein mixtures such as cell lysates, were immobilized on a chip. Avidin- and oligohistidine-tagged proteins can be immobilized within biotin- and Ni-nitrilotriacetic acid-modified gel elements. Most gel-immobilized proteins maintain their biological properties for at least six months. Fluorescence and chemiluminescence microscopy were used as efficient methods for the quantitative analysis of the microchips. Direct on-chip matrix-assisted laser desorption ionization-time of flight mass spectrometry was used for the qualitative identification of interacting molecules and to analyze tryptic peptides after the digestion of proteins in individual gel elements. We also demonstrate other useful properties of protein microchips and their application to proteomics and diagnostics.
Polydimethylsiloxane (PDMS) Sub-Micron Traps for Single-Cell Analysis of Bacteria (2013)

Microfluidics has become an essential tool in single-cell analysis assays for gaining more accurate insights into cell behavior. Various microfluidics methods have been introduced facilitating single-cell analysis of a broad range of cell types. However, the study of prokaryotic cells such as Escherichia coli and others still faces the challenge of achieving proper single-cell immobilization simply due to their small size and often fast growth rates. Recently, new approaches were presented to investigate bacteria growing in monolayers and single-cell tracks under environmental control. This allows for high-resolution time-lapse observation of cell proliferation, cell morphology and fluorescence-coupled bioreporters. Inside microcolonies, interactions between nearby cells are likely and may cause interference during perturbation studies. In this paper, we present a microfluidic device containing hundred sub-micron sized trapping barrier structures for single E. coli cells. Descendant cells are rapidly washed away as well as components secreted by growing cells. Experiments show excellent growth rates, indicating high cell viability. Analyses of elongation and growth rates as well as morphology were successfully performed. This device will find application in prokaryotic single-cell studies under constant environment where by-product interference is undesired.
VH4-34 (VH4.21) gene expression in the chronic arthritides of childhood: studies of associations with anti-lipid A antibodies, HLA antigens, and clinical features. (1996)

The expression of VH4-34 is increased in several rheumatic diseases of childhood, but, as in adults, not in rheumatoid arthritis. VH4-34 expression is not associated with HLA type. The polyspecific autoantibody nature of some VH4-34 derived antibodies may explain the wide range of the unusual antibodies found in oligoarticular arthritis.
Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A 2 (2007)

Ezetimibe, rosuvastatin, and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins. Furthermore, fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2. The clinical implications of these effects remain to be established.
Aminopyrimidines and Derivatives. 20. On the Acetylations of 5-Amino-4-Glycosylmino Pyrimidines (1987)

Abstract The acetylation of 5-amino-4-glycosylamino pyrimidines afforded a wide variety of compounds, depending on the reaction conditions. A systematic study has been carried out and some conclusions with synthetic utility are proposed.
Spatial Heterodyne Imager for Mesospheric Radicals on STPSat‐1 (2010)

The Spatial Heterodyne Imager for Mesospheric Radicals (SHIMMER) was a high‐resolution, near ultraviolet spectrometer that imaged the Earth's limb for 2.5 years between March 2007 and October 2009. The instrument used the Spatial Heterodyne Spectroscopy technique for the first time on a satellite and successfully demonstrated its capabilities. SHIMMER measured the solar resonance fluorescence of the OH A 2 Σ + ‐X 2 Π (0, 0) band around 309 nm, which allows the retrieval of mesospheric OH density profiles. It also measured the Rayleigh scattered background from the clear atmosphere and solar scattering from polar mesospheric cloud particles. We present details on the SHIMMER mission, the payload design, and the data analysis. A comparison between SHIMMER and concurrent Microwave Limb Sounder OH data shows good agreement between 60 and 90 km altitude for several latitudes and seasons. We also find good agreement of the SHIMMER OH densities and standard photochemical model calculations between 60 and 80 km. We find no evidence of a 25%–35% mesospheric OH deficit, previously reported using Middle Atmosphere High‐Resolution Spectrograph Investigation (MAHRSI) OH data. However, independent analysis of Rayleigh scattered background signals observed by SHIMMER and MAHRSI under similar lighting conditions revealed that MAHRSI radiances are systematically smaller than SHIMMER radiances by 24%. Although this difference is well outside of the combined uncertainties for both experiments, the agreement of SHIMMER OH with Microwave Limb Sounder OH and standard photochemistry results, together with our Rayleigh scattering comparison, suggests an unidentified MAHRSI calibration problem that effectively eliminates the mesospheric OH deficit reported using MAHRSI observations.
Dimer destabilization in superoxide dismutase may result in disease-causing properties: Structures of motor neuron disease mutants (2004)

More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body of evidence suggests that a subset of mutations located close to the dimeric interface can lead to a major destabilization of the mutant enzymes. We have determined the crystal structures of the Ala4Val (A4V) and Ile113Thr (I113T) mutants to 1.9 and 1.6 A, respectively. In the A4V structure, small changes at the dimer interface result in a substantial reorientation of the two monomers. This effect is also seen in the case of the I113T crystal structure, but to a smaller extent. X-ray solution scattering data show that in the solution state, both of the mutants undergo a more pronounced conformational change compared with wild-type superoxide dismutase (SOD) than that observed in the A4V crystal structure. Shape reconstructions from the x-ray scattering data illustrate the nature of this destabilization. Comparison of these scattering data with those for bovine CuZn SOD measured at different temperatures shows that an analogous change in the scattering profile occurs for the bovine enzyme in the temperature range of 70-80 degrees C. These results demonstrate that the A4V and I113T mutants are substantially destabilized in comparison with wild-type SOD1, and it is possible that the pathogenic properties of this subset of familial amyotrophic lateral sclerosis mutants are at least in part due to this destabilization.
High performance BDD package by exploiting memory hierarchy (1996)

Article High performance BDD package by exploiting memory hierarchy Share on Authors: Jagesh V. Sanghavi Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CA Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CAView Profile , Rajeev K. Ranjan Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CA Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CAView Profile , Robert K. Brayton Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CA Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CAView Profile , Alberto Sangiovanni-Vincentelli Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CA Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, CAView Profile Authors Info & Claims DAC '96: Proceedings of the 33rd annual Design Automation ConferenceJune 1996 Pages 635–640https://doi.org/10.1145/240518.240638Published:01 June 1996 35citation301DownloadsMetricsTotal Citations35Total Downloads301Last 12 Months5Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
A privatização por omissão: a participação das redes estadual e municipais de educação básica no Rio de Janeiro em 2006 na comparação com as redes privadas (2012)

O estudo compara as matrículas estaduais, municipais e privadas e seus percentuais departicipação na educação básica na média brasileira e na média do Rio de Janeiro em 1997e 2006 e constata que a participação privada média no Rio de Janeiro é maior do que anacional, o que indica uma modalidade de privatização que não tem merecido a devidaatenção, que é a omissão dos governos na oferta de educação em quantidade e qualidadepara todos e, portanto, favorece o mercado das escolas privadas. Esta tem sido umacaracterística dos governos brasileiros (dos mais variados partidos) desde sempre.Entretanto, a omissão não é igual entre os governos. Os governos estaduais e os municipaisdo Rio de Janeiro, por exemplo, demonstram uma omissão muito maior do que a médiados governos estaduais e municipais dos demais estados na oferta de educação básica, e oresultado disso é a maior presença da rede privada no Estado do Rio na comparação com amédia nacional da rede privada em vários níveis e modalidades de ensino. O estudotambém examina a participação das redes estadual, municipais e privadas em cada um dos92 municípios e constata que a maior presença privada se concentra em poucos municípiose é resultado da menor participação do governo estadual (sobretudo no ensino fundamentale no ensino médio regulares) e das prefeituras (sobretudo em creches, pré-escolas e EJA)nestes municípios.
Hierarchical Temporal Memory Method for Time-Series-Based Anomaly Detection (2016)

Time-series-based anomaly detection is a quite important field that has been researched over years. Many techniques have been developed and applied successfully for certain application domains. However, there are still some challenges, such as continuously learning, tolerance to noise and generalization. This paper present Hierarchical Temporal Memory, a novel biological neural network, to time-series-based anomaly detection. HTM is able to learn the changing pattern of the data and incorporate contextual information from the past to make accurate prediction. We have evaluated HTM on real and artificial datasets. The experiment results show that HTM can successfully discover anomalies in time-series data.
Selective Hydrogenation of Cyclopentadiene to Cyclopentene Using Colloidal Palladium Supported on Chelate Resin (1984)

Abstract Cyclopentadiene was hydrogenated to cyclopentene selectively by using colloidal palladium supported on chelate resin with iminodiacetic acid moieties as a catalyst. The catalyst, containing metal particles of 1–6 nm in diameter, was prepared by reduction of the palladium(II)–chelate resin complex with methanol. Cyclopentene was produced in 97.1% yield at 100% conversion of cyclopentadiene at 30 °C under 1 atm of hydrogen. This value in yield was also achieved on repeated uses of the catalyst. The hydrogenation rate was correlated to the polarity parameter, ET(30) values, of the solvents used in the reaction, except in the case of dimethyl sulfoxide. The hydrogenation rates of cyclopentadiene (RD) and cyclopentene (RE) were expressed as RD=kD[H2][catalyst] and RE=kE[H2][cyclopentene][catalyst], respectively, where kD and kE are the rate constants. The equilibrium constant for complex formation between cyclopentadiene and the catalyst, KD, was estimated to be over 400 times larger than that between cyclopentene and the catalyst, KE. A mechanism, including the coordination of olefins to the catalyst and the subsequent hydrogenation of the coordinated complexes, was proposed.
A Randomized Pilot Trial Comparing Cyclosporine and Azathioprine for Maintenance Therapy in Diffuse Lupus Nephritis over Four Years (2006)

There is not agreement about the best maintenance treatment for patients with diffuse lupus nephritis. This multicenter, randomized trial compared the safety and efficacy of cyclosporine and azathioprine. Seventy-five patients with diffuse proliferative lupus were given three intravenous methylprednisolone pulses followed by prednisone and oral cyclophosphamide for a median of 90 d. Subsequently, patients were randomly assigned either to cyclosporine or to azathioprine for 2 yr (core study). Treatment continued for up to 4 yr (follow-up study). The primary outcome measure was the incidence of disease flares. Secondary end points were proteinuria per day, creatinine clearance, and adverse effects. Seven flares occurred in the cyclosporine group, and eight occurred in the azathioprine group. At the end of the core study, mean proteinuria decreased from 2.8 +/- 3.57 to 0.4 +/- 0.85 g/d (P < 0.0001) in the cyclosporine group and from 2.2 +/- 1.94 to 0.5 +/- 0.78 g/d (P < 0.0002) in the azathioprine group. After 4 yr, mean proteinuria was 0.2 +/- 0.24 and 0.3 +/- 0.33 g/d, respectively. At the core study end and at the follow-up completion, creatinine clearance and BP levels did not change significantly from baseline in either group. Five of 36 patients who were receiving cyclosporine and four of the 33 who were receiving azathioprine stopped the treatment because of adverse effects. For patients with diffuse proliferative lupus nephritis, azathioprine or cyclosporine combined with corticosteroids demonstrated equal efficacy in the prevention of flares.
Immunological and Anti-Chaperone Therapeutic Approaches for Alzheimer Disease (2006)

Alzheimer disease (AD) is the most common cause of dementia. Currently available therapies only provide symptomatic relief. A number of therapeutic approaches are under development that aim to increase the clearance of brain Abeta peptides. These include immune mediated clearance of Abeta and the inhibition of the interaction between Abeta and its pathological chaperones. Both active and passive immunization has been shown to have robust effects in transgenic mouse models of AD on amyloid reduction and behavioral improvements. However, a human trial of active immunization has been associated with significant toxicity in a minority of patients. New generation vaccines are being developed which likely will reduce the potential for cell-mediated toxicity. In addition, the recent development of anti-chaperone therapy opens a new therapeutic avenue which is unlikely to be associated with toxicity.