gebhart/patrepeval huggingface dataset:
Measurement of Ventricular Volume by Intracardiac Impedance: Theoretical and Empinrcal Approaches (1986)

The most widely used equation, V = pL2/R, is developed for the computation of ventricular volume from catheter based impedance measurements. The assumptions implicit in this derivation are examined and found to be generally invalid. An empirical discrete resistor model is described which includes the impedance of the myocardial tissue and the adjoining ventricular blood volume. Once the parameters of this model are determined for individual canine hearts, the model predicts stroke volume from measured impedances. Due to the difficulty involved in determining the parameters of the empirical model, a numerical model is developed which solves the equation V σa V U + F = 0 in a three-dimensional volume. This model is then used to determine the effect of parallel tissue resistance, catheter position, and contraction of the other ventricle on volumes computed by intracardiac impedance. Parallel tissue resistance is found to have the greatest impact on absolute volume measurements. However, stroke volume computations are relatively unaffected by any of the three factors.
The safety of liposome bupivacaine following various routes of administration in animals (2015)

Liposome bupivacaine has a favorable safety profile compared with bupivacaine HCl when administered to dogs via intravascular, epidural, and intrathecal routes. This favorable safety profile is likely related to the liposome-bound nature of bupivacaine in the liposome bupivacaine formulation.
Functional expansion of human tRNA synthetases achieved by structural inventions (2009)

Known as an essential component of the translational apparatus, the aminoacyl-tRNA synthetase family catalyzes the first step reaction in protein synthesis, that is, to specifically attach each amino acid to its cognate tRNA. While preserving this essential role, tRNA synthetases developed other roles during evolution. Human tRNA synthetases, in particular, have diverse functions in different pathways involving angiogenesis, inflammation and apoptosis. The functional diversity is further illustrated in the association with various diseases through genetic mutations that do not affect aminoacylation or protein synthesis. Here we review the accumulated knowledge on how human tRNA synthetases used structural inventions to achieve functional expansions.
The Toxicological Assessment of Cyclopentyl Methyl Ether (CPME) as a Green Solvent (2013)

Cyclopentyl methyl ether (CPME) has been used in chemical synthesis as an alternative to hazardous solvents. According to some earlier investigation by others, CPME has low acute or subchronic toxicity with moderate irritation and negative mutagenicity and negative skin sensitization (Local Lymph Node Assay). Calculated Permitted Daily Exposure (PDE) value of CPME obtained by our 28-day oral toxicity test is 1.5 mg/day, and CPME is thus assumed to be a class 2 equivalent solvent in the ICH (International Conference on Harmonization) Harmonized Tripartite Guideline Q3C (R5). Wide synthetic utility and a detailed toxicity study suggest CPME as a green and sustainable solvent of choice for modern chemical transformations.
Proteins and peptides of the salivary gland secretion of medicinal leeches Hirudo verbana, H. medicinalis, and H. orientalis (2008)

The protein and peptide composition of medicinal leech salivary gland secretion (SGS) was analyzed in preparations obtained in July from three species--Hirudo verbana, H. medicinalis, and H. orientalis. Two-dimensional electrophoresis (molecular mass 10-150 kD and pI 3-10) revealed no distinctions in the distribution of over 100 silver-stained proteins. Differences were noted only in intensity of 10 protein spots at 30-90 kD and pI 4.7-7.5. Mass spectrometric profiling of SGS of the three leech species using the Zip-Tip/golden chip scheme and cation-exchanging chips CM-10 revealed over 50 components in SGS of each of the three leech species. It was noted that 30-40% of the individual masses of the SGS of each leech species fall within the masses present in SGS of at least one of the two other species. This rather small part of the total mass may be indicative of a high polymorphism of amino acid sequences or a high frequency of posttranslational modifications of the SGS proteins and peptides. Calculation of Jacquard's coefficient showed that H. medicinalis and H. orientalis are closest to each other in SGS composition, which is consistent with data in the literature on the phylogenetic relationship between these two species of medicinal leech. Comparison of detected molecular masses with those of six known biologically active compounds produced by medicinal leeches revealed their uneven distribution in SGS of each of the three medicinal leech species. This opens prospects for using certain species of medicinal leech for targeted therapy of various pathologies.
In re Haymer. (1983)

Loyola University Medical Center sought a declaratory judgment that a 7-month-old boy was legally dead to permit removal of a mechanical ventilator. The Cook County Circuit Court determined that legal death occurred when the child suffered total and irreversible cessation of all functions of the entire brain and authorized removal of the ventilator. During the appeals process the boy's circulation ceased when his heart failed. In the absence of legislative action, the Illinois appellate court recognized total brain death as the death of a person and added that definition to the common law definition of death, which is cessation of the circulatory and respiratory systems. The court further declared the date of the child's death to be the date of the physicians' determination of brain death.
Exploring Protein–Protein Interactions with Phage Display (2003)

Protein-protein interactions mediate essentially all biological processes. A detailed understanding of these interactions is thus a major goal of modern biological chemistry. In recent years, genome sequencing efforts have revealed tens of thousands of novel genes, but the benefits of genome sequences will only be realized if these data can be translated to the level of protein function. While genome databases offer tremendous opportunities to expand our knowledge of protein-protein interactions, they also present formidable challenges to traditional protein chemistry methods. Indeed, it has become apparent that efficient analysis of proteins on a proteome-wide scale will require the use of rapid combinatorial approaches. In this regard, phage display is an established combinatorial technology that is likely to play an even greater role in the future of biology. This article reviews recent applications of phage display to the analysis of protein-protein interactions. With combinatorial mutagenesis strategies, it is now possible to rapidly map the binding energetics at protein-protein interfaces through statistical analysis of phage-displayed protein libraries. In addition, naïve phage-displayed peptide libraries can be used to obtain small peptide ligands to essentially any protein of interest, and in many cases, these binding peptides act as antagonists or even agonists of natural protein functions. These methods are accelerating the pace of research by enabling the study of complex protein-protein interactions with simple molecular biology methods. With further optimization and automation, it may soon be possible to study hundreds of different proteins in parallel with efforts comparable to those currently expended on the analysis of individual proteins.
Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia (2002)

This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab (R) and fludarabine (F) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia (CLL). The rationale for using R + F includes single-agent efficacy of both drugs, in vitro synergism of R and F, and no apparent overlapping toxicity. Of 31 eligible patients with B-CLL enrolled, 20 were previously untreated and 11 relapsed. Treatment consisted of fludarabine administered at standard doses (25 mg/m(2)/d; days 1-5, 29-33, 57-61, and 85-89) and rituximab (375 mg/m(2)/d) given on days 57, 85, 113, and 151. Side effects such as fever, chills, and exanthema were generally mild (National Cancer Institute Common Toxicity Criteria [NCI-CTC] grade 1/2 in 48% and grade 3 and/or 4 in 3% of patients). Fever and chills were mainly associated with the first rituximab infusion. Hematologic toxicity included neutropenia (grade 1 and/or 2 in 26%, grade 3 and/or 4 in 42%) and thrombocytopenia (grade 1 and/or 2 in 19%, grade 3 and/or 4 in 9%). One patient died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine. There were a total of 32 infections in 16 patients, none of which was fatal. The overall response rate (complete remission [CR] and partial remission [PR]) was 87% (27 of 31 evaluable patients). In 20 previously untreated patients, 17 (85%) responded. Ten of 31 patients achieved CR (5 of 20 untreated; 5 of 11 pretreated; 9 of 21 Binet stage B, 1 of 10 Binet stage C). The median duration of response was 75 weeks. We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL.
Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment (2011)

<h3>Context</h3>Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)–conjugated mammalian recombinant uricase, was developed to fulfill this need.<h3>Objective</h3>To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout.<h3>Design, Setting, and Patients</h3>Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406.<h3>Intervention</h3>Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group).<h3>Main Outcome Measure</h3>Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6.<h3>Results</h3>In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P &lt; .001 and &lt;.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and &lt; .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P &lt; .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008).<h3>Conclusion</h3>Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00325195
Phase II study of mitomycin C, cisplatin and 5-fluorouracil for advanced and recurrent gastric cancer. (2003)

In this study, we assessed the efficacy and feasibility of a 5-FU, MMC and cisplatin combination in patients with advanced or recurrent gastric cancer. 5-FU was administered at a dose of 360 mg/m2 on days 1 through 5 and days 8 through 12. CDDP was administered at a dose of 7 mg/m2 on days 1 through 5 and days 8 through 12. MMC was given at a dose of 13 mg/m2 on day 1. Twenty-seven patients with non-resectable or recurrent gastric cancer were entered. The most common toxicity was leukopenia. Nausea/vomiting was generally mild and no patient suffered severe diarrhea, mucositis or renal insufficiency. While a complete response was not observed, 13 patients showed a PR giving an overall response rate of 48.1% (95%CI, 28.0 to 68.3%). Our regimen may have advantages in terms of reduced toxicity with moderate efficacy that is comparable with results using the ECF regimen.
An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors. (2003)

This study revealed a higher sensitivity of (99m)Tc-TOC as compared with (111)In-OCT as an imaging agent for the localization of SSTR-expressing tumors. To avoid false-positive findings with (99m)Tc-OCT due to nonspecific tracer accumulation, additional scanning at 1-2 h after injection should be done.
ED50 of Intranasal Dexmedetomidine Sedation for Transthoracic Echocardiography in Children with or without a History of Cardiac Surgery for Cyanotic Congenital Heart Disease (2020)

ED50 of intranasal DEX sedation for TTE is similar in children with and without a history of cardiac surgery for cCHD.
Radio resource allocation in fixed broadband wireless networks (1998)

We consider use of fixed broadband wireless networks to provide packet services for telecommuting and Internet access. Each cell is divided into multiple sectors, each of them served by a sector antenna colocated with the base station (BS), and user terminals also use directional antennas mounted on the rooftops of homes or small offices and pointed to their respective BS antennas. To support a target data rate of 10 Mb/s, a bandwidth of several MHz is required. Since radio spectrum is expensive, the bandwidth needs to be reused very aggressively. Thus, efficient strategies for frequency reuse and managing cochannel interference are critically important. We propose several algorithms for dynamic radio-resource allocation in the fixed wireless networks. In particular, a method to be referred to as the staggered resource allocation (SRA) method uses a distributed scheduling algorithm to avoid major sources of interference while allowing concurrent packet transmission and meeting signal-to-interference objectives. The performance of the method is studied by analytic approximations and detailed simulation. Our results show that the combination of directional antennas plus the SRA method is highly effective in controlling cochannel interference. For reasonable system parameters, the SRA method delivers a throughput in excess of 30% per sector while permitting a given frequency band to be reused in every sector of every cell. It also provides satisfactory probability of successful packet transmission. In addition, a simple control mechanism can be applied in the method to improve performance for harsh radio environments.
The ERK Mitogen-Activated Protein Kinase Pathway Contributes to Ebola Virus Glycoprotein-Induced Cytotoxicity (2006)

Ebola virus is a highly lethal pathogen that causes hemorrhagic fever in humans and nonhuman primates. Among the seven known viral gene products, the envelope glycoprotein (GP) alone induces cell rounding and detachment that ultimately leads to cell death. Cellular cytoxicity is not seen with comparable levels of expression of a mutant form of GP lacking a mucin-like domain (GPDeltamuc). GP-induced cell death is nonapoptotic and is preceded by downmodulation of cell surface molecules involved in signaling pathways, including certain integrins and epidermal growth factor receptor. To investigate the mechanism of GP-induced cellular toxicity, we analyzed the activation of several signal transduction pathways involved in cell growth and survival. The active form of extracellular signal-regulated kinases types 1 and 2 (ERK1/2), phospho-ERK1/2, was reduced in cells expressing GP compared to those expressing GPDeltamuc as determined by flow cytometry, in contrast to the case for several other signaling proteins. Subsequent analysis of the activation states and kinase activities of related kinases revealed a more pronounced effect on the ERK2 kinase isoform. Disruption of ERK2 activity by a dominant negative ERK or by small interfering RNA-mediated ERK2 knockdown potentiated the decrease in alphaV integrin expression associated with toxicity. Conversely, activation of the pathway through the expression of a constitutively active form of ERK2 significantly protected against this effect. These results indicate that the ERK signaling cascade mediates GP-mediated cytotoxicity and plays a role in pathogenicity induced by this gene product.
Thermomagnetic residual offset in integrated Hall plates (2003)

Integrated Hall plates show self-induced offset due to the current flow in its current leads. The magnetic field surrounding the current leads causes a magnetic offset signal, while their resistive heating causes thermoelectric offset voltages. This paper reports experimental results on these two effects. They are obtained using a novel test structure enabling one to separate the two contributions.
Nonclinical Safety, Pharmacokinetics, and Pharmacodynamics of Atacicept (2008)

Atacicept, a soluble recombinant fusion protein of the human immunoglobulin (Ig) G(1) Fc and the extracellular domain of the human transmembrane activator and calcium modulator and cyclophylin ligand interactor receptor, acts as an antagonist of both B lymphocyte stimulator and a proliferating-inducing ligand. Here we determined the nonclinical safety, pharmacokinetics and pharmacodynamics of atacicept in mice and cynomolgus monkeys. Subcutaneous atacicept treatment (twice weekly in cynomolgus monkeys, three times weekly in mice) was generally safe and well tolerated safe and well tolerated with dosing up to 10 mg/kg every other day for up to 39 weeks or up to 80 mg/kg when dosed for 4 weeks. At a dose of 1 mg/kg subcutaneous (sc) bioavailability of atacicept in mice and monkeys was 76 and 92%, with a mean serum t(1/2) of 44 and 179 h, respectively. In accord with its anticipated mechanism of action, repeated administration of atacicept decreased serum IgG concentrations up to 50%, IgM concentrations >99%, and circulating mature B-cell concentrations up to 60%. These effects were dose-related but reversible, as determined in a 25-week follow-up period. Microscopically, B cells numbers were reduced in the follicular marginal zone of the spleen and the mantle surrounding germinal centers of the lymph nodes. These data confirm the preclinical safety and the pharmacological activity of atacicept and support its clinical development.
HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression genes during lymphoid tumorigenesis (2011)

We found that HMGA1 induces inflammatory pathways early in lymphoid tumorigenesis and pathways involved in stem cells, cell cycle progression, and cancer in established tumors. HMGA1 also dyregulates genes and pathways involved in stem cells, cellular development and hematopoiesis at both early and late stages of tumorigenesis. These results provide insight into HMGA1 function during tumor development and point to cellular pathways that could serve as therapeutic targets in lymphoid and other human cancers with aberrant HMGA1 expression.
Serine Protease Mechanism and Specificity (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSerine Protease Mechanism and SpecificityLizbeth HedstromView Author Information Department of Biochemistry, MS 009, Brandeis University, Waltham, Massachusetts 02454 Cite this: Chem. Rev. 2002, 102, 12, 4501–4524Publication Date (Web):November 23, 2002Publication History Received14 May 2002Published online23 November 2002Published inissue 1 December 2002https://pubs.acs.org/doi/10.1021/cr000033xhttps://doi.org/10.1021/cr000033xresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views31420Altmetric-Citations1390LEARN 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 SUBJECTS:Chemical specificity,Hydrolysis,Monomers,Noncovalent interactions,Peptides and proteins Get e-Alerts
Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia* (2004)

Neurotensin-induced hypothermia improved neurologic outcome after asphyxial cardiac arrest in rats vs. brief external cooling but was comparable to prolonged external cooling.
Elevated and Deregulated Expression of HDAC3 in Human Astrocytic Glial Tumours (2006)

Abnormal expression of histone deacetylases may contribute to the establishment of a cancer specific transcription profile. We examined expression of HDAC3 in human non-malignant gliosis and glial astrocytic tumours. Samples from four non-malignant gliosis and 17 astrocytic gliomas (six of grade II, one of grade III and ten of grade IV) removed for therapeutic purposes were assayed for HDAC3 expression at mRNA and protein levels. HDAC3 mRNA was detected in non-tumorous gliosis as well as in all examined glial tumours. Seven out of eleven examined high-grade tumours showed an elevated number of copies of HDAC3 mRNA. Western blot analysis detected high levels of expression of HDAC3 in the majority of the examined tumours. Immunohistochemistry and immunofluorescence made on a collection of 35 astrocytic tumours detected nuclear as well as cytoplasmic HDAC3 expression in all of those tumours. While the distribution of HDAC3 was both nuclear as well as cytoplasmic and moderate in intensity in non-malignant tissues and low-grade gliomas, high-grade tumours expressed HDAC3 in a focally deregulated pattern that included strongly pronounced cytoplasmic localization. Confocal microscopy and additional co-localization analysis detected nuclear HDAC3 in all tumours examined. We conclude that HDAC3 expression is elevated in human astrocytic tumours and its expression pattern is deregulated at the cellular level in high-grade gliomas.