gebhart/patrepeval huggingface dataset:
A Study of Dylan Thomas’s Poetry (2012)

Dylan Thomas is one of the writers who has often been associated with Welsh literature and culture in the last sixty years. He is possibly the most notable Welsh author. Fortunately, it is mainly his literary work, and not his tumultuous lifestyle, that is still associated with him. The analysis of some of his poems mirrors his sincere relationship to Wales. In 1937 he married to Caitlin MacNamara who gave birth to three children. These circumstances indicate a typical British conservative and straight forward approach to family life. Dylan Thomas was influenced in his writing by the Romantic Movement for the beginning of the nineteenth century and this can be seen in a number of his best works. Dylan Thomas uses symbols and images of nature to express how he feels towards death and childhood. He says that images are used to create a feeling of love towards life. Despite Dylan Thomas's obscure images, he expresses a clear message of religious devotion in many of his poems. The style of Dylan Thomas is an opaque poetic style which Thomas used to perfection. He possessed tremendous talent
NK- and CD8+ T Cell-Mediated Eradication of Established Tumors by Peritumoral Injection of CpG-Containing Oligodeoxynucleotides (2001)

Unmethylated cytosine-phosphorothioate-guanine (CpG) containing oligodeoxynucleotides (CpG-ODN) are known to act as adjuvants and powerful activators of the innate immune system. We investigated the therapeutic effect of CpG-ODN on a variety of established mouse tumors including AG104A, IE7 fibrosarcoma, B16 melanoma, and 3LL lung carcinoma. These tumors are only weakly immunogenic and notoriously difficult to treat. Repeated peritumoral injection of CpG-ODN resulted in complete rejection or strong inhibition of tumor growth, whereas systemic application had only partial effects. The CpG-ODN-induced tumor rejection was found to be mediated by both NK and tumor-specific CD8(+) T cells. Comparison of parental tumors and variants rendered more antigenic by transfection with tumor Ags suggested that the efficiency of the CpG-ODN therapy correlated with the antigenicity of the tumors. Peritumoral CpG-ODN treatment was even effective in a situation where the immune system was tolerant for the tumor Ag, as shown by breakage of tolerance and tumor elimination. These results suggest that peritumoral application of CpG-ODN acts locally by inducing NK cells, and also leads to efficient presentation of tumor Ags and stimulation of CD8(+) effector and memory T cells, thus providing a powerful antitumor therapy that can be also applied without knowledge of the tumor Ag.
Ultrasonic displacement and strain imaging of coronary arteries with a catheter array (2002)

Tissue elasticity can be estimated from displacement and strain images acquired under controlled deformation. We extend this approach for coronary arteries, deformed and imaged by an integrated angioplasty balloon and ultrasonic imaging probe. Because the lumen cross section of a severely occluded artery is generally not circular, we have also developed a technique to perform all motion computations in the reference frame of the lumen's geometric center. This coordinate system is independent of the imaging catheter, and consequently referencing to this frame removes artifacts associated with probe motion within the balloon during deformation. Displacements and strains estimated by phase-sensitive correlation-based speckle tracking were used to distinguish arterial plaques in simulated coronary arteries of differing elastic moduli: hard, soft, and homogenous. We have also applied these methods to images of a homogeneous gelatin phantom collected with the integrated probe. The spatial dependence of these quantities shows good agreement with theoretically predicted values.
A phase Ib study of the anti-cancer stem cell agent demcizumab (DEM) & gemcitabine (GEM) +/- paclitaxel protein bound particles (nab-paclitaxel) in pts with pancreatic cancer. (2015)

4118 Background: Delta-like ligand 4 (DLL4) activates the Notch pathway. DEM is a humanized IgG2anti-DLL4 antibody that inhibits tumor growth & decreases cancer stem cell frequency in human tumor xenograft models. In addition, DEM has an antiangiogenic effect & synergistic activity when combined with GEM & nab-paclitaxel in pt derived xenograft models of pancreatic cancer. Methods: Pts with 1st line pancreatic cancer were enrolled. Pts in cohorts 1-3 received DEM (2.5 every 2 or 4 wks or 5 mg/kg every 4 wks including 3 truncated pts) & GEM 1000 mg/m2 7 of 8 wks, then 3 of 4 wks. Pts in cohorts 4, 5 & 6 received truncated DEM (2.5, 3.5 or 5 mg/kg every 2 wks through Day 70) & nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m23 of 4 wks. The primary objective was to determine the MTD. Other objectives were safety, efficacy, immunogenicity, PK & biomarkers. Results: 47 pts were enrolled; 8, 8, 8, 6, 8 & 9 pts received 2.5 mg/kg every 2 wks, 2.5 mg/kg every 4 wks, 5 mg/kg every 4 wks, 2.5 mg/kg every 2 wks (truncated), 5 mg/kg every 2 wks (truncated) & 3.5 mg/kg every 2 wks (truncated), respectively. Related AEs in > 20% of pts were fatigue (38%), nausea (34%), vomiting (28%), decreased appetite (21%), hypertension (21%) & diarrhea (21%). Hypertension was managed with anti-hypertensives. Increased BNP is an early indicator of the cardiac effects of DEM & mildly elevated values were used to initiate cardioprotective therapy with an ACE inhibitor or carvedilol. One pt who received 5 mg/kg continuously developed reversible pulmonary hypertension & heart failure on day 143. As a result, DEM was limited to 70 days in cohorts 4, 5 & 6. In cohorts 1-3, 4 of 16 (25%) pts had a PR & 7 had SD. In cohorts 4, 5 & 6, 9 of 22 (41%) pts had a PR & 10 had SD. The median PFS for 2.5 & 5 mg/kg every 4 wks & 2.5 mg/kg, 2.5 mg/kg (truncated), 3.5 (truncated) & 5 mg/kg (truncated) every 2 wks were 1.7, 7, 3.4, 9.1, not reached & not reached, respectively. Conclusions: This therapy was generally well tolerated with fatigue, nausea & vomiting being the most common related AEs. Encouraging clinical activity was observed. Biomarker analysis showed pharmacodynamic modulation of the Notch pathway. Final data will be presented. Clinical trial information: NCT01189929.
Abstract 4529: Pharmacokinetics (PK) of LOXO-101 during the first-in-human Phase I study in patients with advanced solid tumors: Interim update (2015)

Abstract Background LOXO-101 is the first highly selective and potent small-molecule inhibitor of TRKA, TRKB, and TRKC to be dosed clinically. It has approximately 100-fold selectivity over other kinase and non-kinase targets. We report here the interim results of the first-in-man Phase I study which evaluates the safety, maximum-tolerated dose (MTD), and PK of LOXO-101 in patients with advanced solid tumors. Methods This is an ongoing open-label, multicenter, 3+3 dose escalation Phase I study of LOXO-101. Patients with solid tumors refractory to standard therapy, with normal hematopoietic and major organ function were eligible for study. LOXO-101 was administered orally as a single dose, followed by QD or BID doses for continuous 28-day cycles. Receptor occupancy was determined with an Emax model based on unbound LOXO-101 plasma concentrations. Results To date, data are available for 8 patients including patients treated at each of the first two dose levels, 50 mg QD and 100 mg QD. LOXO-101 has been well tolerated; the MTD has not been reached and no adverse events have been reported more than once other than fatigue (two patients; related but not serious) and syncope (two patients; unrelated and serious). Maximum plasma concentrations of LOXO-101 were reached 30-60 minutes following dosing and exposure increased in approximate proportion with dose. Mean values of Cl/F, V/F, and half-life were 0.5 L/h/kg, 2 L/kg, and 3.5 h, respectively, and were independent of dose. Exposure was similar following the single dose and on Day 1 and Day 8 of repeated dosing in all subjects. The unbound drug levels of LOXO-101 appear sufficient for approximately 98% inhibition of TRKA/B/C at peak concentrations with once-daily dosing of 50 or 100 mg. Conclusions LOXO-101 has been well tolerated and has sufficient systemic exposure for robust inhibition of the TRKA, TRKB, and TRKC kinases without inhibition of other kinases. With dose escalation continuing, additional data and follow up will be provided at time of presentation. Citation Format: Howard A. Burris, Alice T. Shaw, Todd M. Bauer, Anna F. Farago, Robert C. Doebele, Steven Smith, Nisha Nanda, Scott Cruickshank, Jennifer A. Low, Marcia S. Brose. Pharmacokinetics (PK) of LOXO-101 during the first-in-human Phase I study in patients with advanced solid tumors: Interim update. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4529. doi:10.1158/1538-7445.AM2015-4529
Prolonged use of dexmedetomidine in an infant with respiratory failure following living donor liver transplantation (2006)

We used dexmedetomidine for more than 2 months in a mechanically ventilated infant without serious adverse effects. An infant with liver cirrhosis of unknown cause underwent living donor liver transplantation at the age of 9 months. Long-term mechanical ventilation was required postoperatively, and midazolam with fentanyl had been used to sedate the patient. They required increase to 1.7 mg.kg(-1).h(-1) and 3.5 microg.kg(-1).h(-1), respectively, which were still inadequate. On postoperative day 29, dexmedetomidine was added. The rate of dexmedetomidine infusion was increased gradually to 1.4 microg.kg(-1).h(-1). It was discontinued temporarily to exclude drug-induced liver dysfunction. However, without dexmedetomidine, adequate sedation level was unattainable. Liver dysfunction was likely to be attributed to cytomegalovirus infection and after restarting dexmedetomidine, the respiratory condition improved. He was extubated 10 weeks after the operation. Dexmedetomidine was successfully tapered off over the following 2 weeks with no signs of withdrawal. Dexmedetomidine was a useful sedative for an infant who required mechanical ventilation for a prolonged period of time.
Dendrimer Internalization and Intracellular Trafficking in Living Cells (2010)

The ability of dendrimers to cross cell membranes is of much interest for their application in drug and gene delivery. Recent studies demonstrate that dendrimers are capable to enter cells by endocytosis, but the intracellular pathway following their internalization remains controversial. In this study we use confocal fluorescence microscopy to elucidate the intracellular trafficking properties of PAMAM dendrimers with high spatial and temporal resolution in living HeLa cells. Macromolecules of different chemical functionality (neutral, cationic and lipidated), size (from G2 up to G6) and surface charge are investigated and their internalization properties correlated with the molecular structure. Toxicity and internalization data are discussed that allow the identification of dendrimers maximizing intracellular uptake with the minimum effect on cell viability. Time-lapse imaging and colocalization assays with fluorescent biomarkers for endocytic vesicles demonstrate that dendrimers are internalized by both clathrin-dependent endocytosis and macropinocytosis and are eventually delivered to the lysosomal compartment. Moreover we analyzed the uptake of dendrimers in additional cell lines of practical interest for therapeutic purposes. These measurements together with a direct comparison with TAT peptides demonstrate that PAMAM dendrimers possess similar properties to these widely used cell-penetrating peptides and thanks to their chemical tunability may represent a valid alternative for drug and gene delivery.
The American Society of Hematology: a success at age 50; blood banking and sodium citrate (2008)

To the editor:

I enjoyed the excellent article by Drs Jaffe and Kaushansky, “The American Society of Hematology: a success at age 50.”[1][1]

There is some controversy concerning the introduction of sodium citrate for blood transfusion and the establishment of the first blood bank in the United
Robot multiple contact control (2008)

SUMMARY This paper addresses the problem of contact force control for multiple contacts distributed over multiple links in a robot. This is of importance when performing complex tasks in unstructured environment, particularly in humanoid robot applications. The proposed multicontact control framework provides a new way of defining the operational space coordinates, which facilitates the specification of multiple contact control. The contact force space on multiple links is constructed as an operational space for the highest priority task. Motion control, given lower priority, can be executed using the rest of degree of freedom within the null-space of the force control. The dynamic control structure, then, provides a means to control each contact force and motion independently. This dynamic decoupling enables each contact force controller to utilize linear control theories. In particular, the contact force controllers adopt full state feedback control and estimation methods to produce robust performance with respect to modeling and parameter uncertainties. The effectiveness of the multiple contact control framework was demonstrated using a PUMA560 manipulator, with multiple contacts on the end-effector and third link. The demonstrated tasks involved controlling each of the contact forces with null-space motion.
Evidence That CYP2C19 is the Major (S)-Mephenytoin 4'-Hydroxylase in Humans (1994)

The present study assesses the role of members of the human CYP2C subfamily in the 4'-hydroxylation of (S)-mephenytoin. When recombinant CYP2C proteins were expressed using a yeast cDNA expression system, 2C19 stereospecifically 4'-hydroxylated (S)-mephenytoin with a turnover number at least 10 times higher than that of human liver microsomes. 2C9 (both Ile359 and Leu359 alleles) and 2C18 (Thr385 and Met385 alleles) metabolized this substrate at a rate 100-fold lower than 2C19, and metabolism by these 2C proteins was not stereospecific for the S-enantiomer. 2C8 exhibited very little mephenytoin 4'-hydroxylase activity. In contrast, the Ile359 allele of 2C9 had a high turnover number for the hydroxylation of tolbutamide, while the Leu359 allele was less active toward this substrate. Immunoblot analysis of 16 human liver donor samples indicated that (S)-mephenytoin 4'-hydroxylase activity correlated with the hepatic CYP2C19 content, but it did not correlate with the hepatic content of CYP2C9. Moreover, direct sequencing of the polymerase chain reaction (PCR) products of 2C9 mRNA from six of these human livers through areas of known allelic variations indicated that the identity of the allele of 2C9 (Cys144 vs Arg, Tyr358 vs Cys, Ile359 vs Leu, or Gly417 vs Asp) did not appear to influence (S)-mephenytoin 4'-hydroxylase activity in these samples. These data indicate that 2C19 is the principal determinant of (S)-mephenytoin 4'-hydroxylase activity in human liver.
4-1BB Ligand as an Effective Multifunctional Immunomodulator and Antigen Delivery Vehicle for the Development of Therapeutic Cancer Vaccines (2010)

Therapeutic subunit vaccines based on tumor-associated antigens (TAA) represent an attractive approach for the treatment of cancer. However, poor immunogenicity of TAAs requires potent adjuvants for therapeutic efficacy. We recently proposed the tumor necrosis factor family costimulatory ligands as potential adjuvants for therapeutic vaccines and, hence, generated a soluble form of 4-1BBL chimeric with streptavidin (SA-4-1BBL) that has pleiotropic effects on cells of innate, adaptive, and regulatory immunity. We herein tested whether these effects can translate into effective cancer immunotherapy when SA-4-1BBL was also used as a vehicle to deliver TAAs in vivo to dendritic cells (DCs) constitutively expressing the 4-1BB receptor. SA-4-1BBL was internalized by DCs upon receptor binding and immunization with biotinylated antigens conjugated to SA-4-1BBL resulted in increased antigen uptake and cross-presentation by DCs, leading to the generation of effective T-cell immune responses. Conjugate vaccines containing human papillomavirus 16 E7 oncoprotein or survivin as a self-TAA had potent therapeutic efficacy against TC-1 cervical and 3LL lung carcinoma tumors, respectively. Therapeutic efficacy of the vaccines was associated with increased CD4(+) T and CD8(+) T-cell effector and memory responses and higher intratumoral CD8(+) T effector/CD4(+)CD25(+)Foxp3(+) T regulatory cell ratio. Thus, potent pleiotropic immune functions of SA-4-1BBL combined with its ability to serve as a vehicle to increase the delivery of antigens to DCs in vivo endow this molecule with the potential to serve as an effective immunomodulatory component of therapeutic vaccines against cancer and chronic infections.
Involvement of Chemokine Receptor 4/Stromal Cell–Derived Factor 1 System during Osteosarcoma Tumor Progression (2005)

Despite intensive chemotherapy and surgery treatment, lung and bone metastasis develop in about 30% of patients with osteosarcoma. Mechanisms for this preferential metastatic behavior are largely unknown. We investigated the role of the chemokine receptor 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) system to drive the homing of osteosarcoma cells. We analyzed the expression of the CXCR4 and SDF-1 proteins on several osteosarcoma cell lines and the effects of SDF-1 on migration, adhesion, and proliferation of these cancer cells. In vitro assays showed that the migration of osteosarcoma cells expressing CXCR4 receptor follows an SDF-1 gradient and that their adhesion to endothelial and bone marrow stromal cells is promoted by SDF-1 treatment. Moreover, the production of matrix metalloproteinase-9 is increased after SDF-1 exposure. We finally proved in a mouse model our hypothesis of the CXCR4/SDF-1 axis involvement in the metastatic process of osteosarcoma cells. Development of lung metastasis after injection of osteosarcoma cells was prevented by the administration of a CXCR4 inhibitor, the T134 peptide. These data show a possible explanation for the preferential osteosarcoma metastatic development into the lung, where SDF-1 concentration is high, and suggest that molecular strategies aimed at inhibiting the CXCR4/SDF-1 pathway, such as small-molecule inhibitors or anti-CXCR4 antibodies, might prevent the dissemination of osteosarcoma cells.
Immunochemical Studies on Normal and Tay-Sachs'Brain Gangliosides. (1966)

Gangliosides from normal human, Tay-Sachs' and beef brain tissues administered intramuscularly with Freund's adjuvant, caused the production of precipitating antibodies in 15 out of 16 rabbits. Agar double diffusion analysis showed the presence of 2–3 or more precipitin bands in the reaction of each antigen with its homologous antiserum. Antiserum to normal human brain gangliosides formed only one precipitin band with gangliosides from Tay-Sachs' brain, while antiserum to gangliosides from Tay-Sachs' brain did not cross react with the gangliosides from normal brain. A purified monosialoganglioside from Tay-Sachs' brain gave one precipitin band only with the antiserum to gangliosides extracted from Tay-Sachs' brain.
Optimization of docosahexaenoic acid (DHA) production and improvement of astaxanthin content in a mutant Schizochytrium limacinum isolated from mangrove forest in Thailand (2007)

Polyunsaturated fatty acids including DHA are essential dietary fatty acids. At present, fish oils are a major source, but an alternative supply is needed because of increasing demand and fish dwindling stocks. This need might be satisfied using a thraustochytrids found in mangrove forests of Thailand and identified by 18S rDNA sequencing as either Schizochytrium limacinum or Thraustochytrium aggregatum. S. limacinum was tested in various culture conditions to find the optimal yield of DHA. This culture medium contained 7.5% glucose, 0.5% peptone, 0.5% yeast extract (with either 0.25% soybean meal or 1% skimmed milk) and 0.75% sea salt at 20-30°C. The C:N ratio was about 15:1. The culture was mutated using NTG and one isolate showed high DHA content and also a red pigment identified as astaxanthin by TLC and HPLC. Astaxanthin synthesis peaked on day 6 - 10 of incubation in medium containing 2% glucose using shaking flasks at 180 rpm, 25°C, 2 kLux light intensity with a 18:6 h light:dark periods. Six days of incubation yielded the highest yields of both DHA (224.6 mg/l) and astaxanthin (8.9 µg/ml of medium). These results suggested that this microorganism could provide
Properties of the Reverse Transcription Reaction in mRNA Quantification (2004)

RT-QPCR gene expression measurements are comparable only when the same priming strategy and reaction conditions are used in all experiments and the samples contain the same total amount of RNA. Experimental accuracy is improved by running samples in (at least) duplicate starting with the reverse transcription reaction.
Lipid metabolome-wide effects of the PPARγ agonist rosiglitazone (2002)

Successful therapy for chronic diseases must normalize a targeted aspect of metabolism without disrupting the regulation of other metabolic pathways essential for maintaining health. Use of a limited number of single molecule surrogates for disease, or biomarkers, to monitor the efficacy of a therapy may fail to predict undesirable side effects. In this study, a comprehensive metabolomic assessment of lipid metabolites was employed to determine the specific effects of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone on structural lipid metabolism in a new mouse model of Type 2 diabetes. Dietary supplementation with rosiglitazone (200 mg/kg diet) suppressed Type 2 diabetes in obese (NZO x NON)F1 male mice, but chronic treatment markedly exacerbated hepatic steatosis. The metabolomic data revealed that rosiglitazone i) induced hypolipidemia (by dysregulating liver-plasma lipid exchange), ii) induced de novo fatty acid synthesis, iii) decreased the biosynthesis of lipids within the peroxisome, iv) substantially altered free fatty acid and cardiolipin metabolism in heart, and v) elicited an unusual accumulation of polyunsaturated fatty acids within adipose tissue. These observations suggest that the phenotypes induced by rosiglitazone are mediated by multiple tissue-specific metabolic variables. Because many of the effects of rosiglitazone on tissue metabolism were reflected in the plasma lipid metabolome, metabolomics has excellent potential for developing clinical assessments of metabolic response to drug therapy.
Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway (2007)

CD4(+) helper T (Th) cells play a crucial role in the delicate balance between host defense and autoimmune disease. Two important populations of helper T cells are the proinflammatory, interleukin-17 (IL-17)-producing (Th17) cells and the anti-inflammatory forkhead box P3-positive (FoxP3(+)) T regulatory (Treg) cells. Here we show that all-trans retinoic acid (ATRA) and other agonists of the retinoic acid receptor alpha (RARalpha) inhibit the formation of Th17 cells and promote FoxP3 expression. Conversely, inhibition of retinoic acid signaling constrains transforming growth factor beta (TGF-beta1) induction of FoxP3. The effect of ATRA is mediated independently of IL-2, signal transducer and activator of transcription 5 (Stat5) and Stat3, representing a novel mechanism for the induction of FoxP3 in CD4 T cells. As previous studies have shown that vitamin A derivatives are protective in animal models of autoimmune disease, the current data suggest a previously unrecognized role for RARalpha in the regulation of CD4(+) T-cell differentiation and provide a mechanism for the anti-inflammatory effects of retinoic acid.