gebhart/patrepeval huggingface dataset:
Controlled/“Living” Radical Polymerization. Homogeneous Reverse Atom Transfer Radical Polymerization Using AIBN as the Initiator (1997)

Atom transfer radical polymerization using AIBN/CuBr2/2dNbipy as the initiating system has been successfully carried out for styrene, methyl acrylate, and methyl methacrylate. Well-defined polymers with low polydispersities have been obtained. High apparent initiation efficiencies were observed for both styrene and methyl acrylate polymerizations at 110 °C. With an increase of the [AIBN]o/[CuBr2/2dNbipy]o ratio, apparent initiation efficiency decreased and polydispersity increased. Low initiation efficiencies were observed for the polymerizations of methyl methacrylate at both 110 and 90 °C, with higher polydispersities at higher temperature. The changes in polydispersity with respect to the changes in [AIBN]o/[CuBr2/2dNbipy]o ratio and the temperature can be explained by the differences in the rate of deactivation by the copper(II) halide species.
The GLP-1 Derivative NN2211 Restores β-Cell Sensitivity to Glucose in Type 2 Diabetic Patients After a Single Dose (2003)

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion in a glucose-dependent manner, but its short half-life limits its therapeutic potential. We tested NN2211, a long-acting GLP-1 derivative, in 10 subjects with type 2 diabetes (means +/- SD: age 63 +/- 8 years, BMI 30.1 +/- 4.2 kg/m(2), HbA(1c) 6.5 +/- 0.8%) in a randomized, double-blind, placebo-controlled, crossover study. A single injection (7.5 micro g/kg) of NN2211 or placebo was administered 9 h before the study. beta-cell sensitivity was assessed by a graded glucose infusion protocol, with glucose levels matched over the 5-12 mmol/l range. Insulin secretion rates (ISRs) were estimated by deconvolution of C-peptide levels. Findings were compared with those in 10 nondiabetic volunteers during the same glucose infusion protocol. In type 2 diabetic subjects, NN2211, in comparison with placebo, increased insulin and C-peptide levels, the ISR area under the curve (AUC) (1,130 +/- 150 vs. 668 +/- 106 pmol/kg; P < 0.001), and the slope of ISR versus plasma glucose (1.26 +/- 0.36 vs. 0.54 +/- 0.18 pmol x l[min(-1) x mmol(-1) x kg(-1)]; P < 0.014), with values similar to those of nondiabetic control subjects (ISR AUC 1,206 +/- 99; slope of ISR versus plasma glucose, 1.44 +/- 0.18). The long-acting GLP-1 derivative, NN2211, restored beta-cell responsiveness to physiological hyperglycemia in type 2 diabetic subjects.
Craze growth and healing in polystyrene (1987)

Abstract The kinetics of craze growth and craze healing were studied by dark‐field optical microscopy in monodisperse molecular weight polystyrene (PS) that varied in molecular weight from 88,000 to 1,334,000. The following observations were made. (1) G 1 the virgin growth rate, decreased rapidly with increasing molecular weight until M n ∼ 200,000 and then remained constant. (2) G 1 decreased with increasing craze density. (3) The growth rates of approaching craze tips decreased when the craze tips overlapped, and the effect was less for crazes whose parallel growth paths were greater than 40 μm apart. (4) Complete craze healing was observed by comparison of the nucleation times, τ 2 , and growth rates, G 2 , of healed individual crazes with the craze kinetics of the virgin sample. (5) The extent of healing was characterized using four cases in which τ and G were measured as a function of healing time, temperature, constant stress, and molecular weight. (6) Craze healing times were found to increase with molecular weight and were analyzed in terms of the modified molecular weight of the craze zone. (7) Significant bond rupture was determined to occur during crazing by comparison of healing times with stress relaxation and diffusion data. (8) Craze healing studies provide insight into both crack healing and fracture of glassy polymers.
Childhood leukaemia: a relationship between intracellular 6‐ mercaptopurine metabolites and neutropenia. (1983)

6‐Mercaptopurine is extensively used in the treatment of childhood lymphoblastic leukaemia to prolong the duration of remission achieved with other drugs. The response to remission maintenance therapy varies widely. We investigated the relationship between red blood cell 6‐ thioguanine nucleotide, a metabolite of 6‐mercaptopurine, and myelosuppression in 22 children with acute lymphoblastic leukaemia in remission. The peripheral neutrophil count was used as an index of myelosuppression. 6‐Mercaptopurine dose was related to 6‐thioguanine nucleotide concentration (r = 0.4; P less than 0.001; n = 90; y = 18.51 + 0.36 x). Large individual variations around the regression line are observed. Neither 6‐mercaptopurine dose nor 6‐thioguanine nucleotide concentration was related to the neutrophil count at the time of sampling (day 0) or 7 days later. Both 6‐mercaptopurine dose and 6‐ thioguanine nucleotide concentration correlated with the neutrophil count at day 14 (r = −0.33; P less than 0.01; n = 90 and r = −0.3; P less than 0.01; n = 90 respectively). This delay is compatible with a cytotoxic action on bone marrow stem cells. Excluding children with other, uncontrolled, potentially myelosuppressive influences the correlation between 6‐thioguanine nucleotide concentration and neutropenia improved (r = −0.6; P less than 0.001; n = 37). A significant degree of neutropenia was observed by day 14 if the 6‐ thioguanine nucleotide concentration (day 0) was greater than 210 pmol/8 × 10(8) RBCs. The assay of 6‐thioguanine nucleotide may highlight those individuals with pharmacokinetic resistance. Two children on continuous high dose 6‐mercaptopurine, had low red blood cell 6‐thioguanine nucleotide concentrations and neutropenia was not observed.
Characterization and Solid-State Transformations of the Pseudopolymorphic Forms of Sodium Naproxen (2004)

Sodium naproxen is an antiinflammatory nonsteroidal drug used in the treatment of rheumatoid and arthritic diseases. Three pseudopolymorphic forms have been reported in the literature, along with characterizations of anhydrous and dihydrated forms. In the present work, the monohydrated form of sodium naproxen was prepared by dehydration of the dihydrated form and investigated with thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and microscopy. Characteristic properties of the monohydrated form were compared to the anhydrous and the dihydrated forms, and the transformation of higher hydrated forms to lower ones was performed in an oven or a desiccator without generating other polymorphic forms. DSC and isothermal TGA experiments determined the structural characteristics and mechanisms by which two types of water were removed from the hydrated species.
Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma (1990)

A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha- methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma.
Safety and immunogenicity of a nicotine conjugate vaccine in current smokers (2005)

Immunotherapy is a novel potential treatment for nicotine addiction. The aim of this study was to assess the safety and immunogenicity of a nicotine conjugate vaccine, NicVAX, and its effects on smoking behavior. Smokers (N = 68) were recruited for a noncessation treatment study and assigned to 1 of 3 doses of the nicotine vaccine (50, 100, or 200 microg) or placebo. They were injected on days 0, 28, 56, and 182 and monitored for a period of 38 weeks. Results showed that the nicotine vaccine was safe and well tolerated. Vaccine immunogenicity was dose-related (P < .001), with the highest dose eliciting antibody concentrations within the anticipated range of efficacy. There was no evidence of compensatory smoking or precipitation of nicotine withdrawal with the nicotine vaccine. The 30-day abstinence rate was significantly different across the 4 doses (P = .02), with the highest rate of abstinence occurring with 200 microg. The nicotine vaccine appears to be a promising medication for tobacco dependence.
The influence of the degree of maturation of donor tissue on the reconstruction of elastic cartilage by isolated chondrocytes (1977)

Chondrocytes isolated from auricular cartilage of 1-, 14-, 28- and 56-day-old rabbits were injected intrasmuscularly as auto- or allogeneic transplants, and the development of the reconstructed cartilage was compared to that of intact tissue. Chondrocytes in cartilage of 1- and 14-day-old rabbits (younger group) were relatively uniform in size. During further development in situ (28 and 56 days) central cells increased considerably and many of them became binucleated. Cartilage reconstructed by chondrocytes from the younger group of animals displayed regular arrangement of cells, i.e. smaller cells at the periphery and larger in the centre. Transplantation of chondrocytes from 28 or 56-day-old rabbits (older group) led to the reconstruction of cartilage with irregular distribution of cells, i.e. some large cells were located at its periphery, while in the centre smaller and larger cells were intermingled in a haphazard manner. Elastic fibres were scanty and thin in cartilage of 1-day-old animals, but their number and size increased with time and they displayed a characteristic pattern. Formation and maturation of these fibres proceeded in cartilage reconstructed by chondrocytes from the younger gorup of animals similarly as in the intact tissue. Chondrocytes from the older group of rabbits reconstructed cartilage in which the number of elastic fibres was reduced and their arrangement appeared irregular.
Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? (2012)

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9)-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9)-tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.
Antibiotics from Micromonospora (1980)

AMINOGL YCOSIDES . Gentamicins ...... . . ..... . . . . . . . . . . . . . . . ........ . . .. . . .. .. . .. . . . .. ... . ......... . . . . . .. . .. . . .. . .. . . ... . . . . . . ... . Sisomicin . Verdamicin . Antibiotic G-52 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antibiotic G-4 I 8 . Antibiotic 1/-20 . Fortimicins . Neomycin . Antibiotic 460 . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . Sagamicin .... . .. . . .. . . .. . . . .. . . . . . . . . ... ..... .... ....... . . . .. ... . . . ... . . . . . . . ....... . . . . .. . .. . .. . .. . . .. . . . .. . . . .. . .. . . .. . . . MACROLIDES .
Phase I trial of zalutumumab and irinotecan in metastatic colorectal cancer patients who have failed irinotecan- and cetuximab-based therapy (2009)

e15028 Background: Zalutumumab is a novel human IgG1 anti-EGFR mAb. We investigated the safety of zalutumumab and irinotecan in heavily pretreated mCRC patients. Methods: Metastatic CRC patients with documented progression (PD) during or within 6 months of stopping cetuximab and irinotecan based therapy were eligible. No prior treatment with anti-EGFR antibodies other than cetuximab was allowed. Patients received weekly doses of zalutumumab 8mg/kg and 16 mg/kg respectively in combination with irinotecan (180 mg/m 2 ) every second week until PD or unacceptable toxicity. Results: The maximum tolerated dose was not reached and no patients experienced any dose limiting toxicity. At data cut-off (18-Dec-08) 4 patients had died (no cases of death were considered related to zalutumumab), 4 were off study due to PD and 1 was still ongoing ( Table 1 ). In total, 6 patients experienced one or more grade 3/4 toxicities (diarrhea 2; neutropenia 2; leucopenia 1; abdominal pain 1; pulmonary embolism 1; alopecia 1). Conclusions: Zalutumumab can be safely administrated in doses up to 16mg/kg in combination with irinotecan in mCRC patients failing cetuximab and irinotecan based therapy. Zalutumumab and irinotecan resulted in durable stable disease warranting further investigation of this regimen. [Table: see text] [Table: see text]
JAK3 Inhibition Significantly Attenuates Psoriasiform Skin Inflammation in CD18 Mutant PL/J Mice (2009)

JAK3, a member of the Janus kinase family, is predominantly expressed in hemopoietic cells and binds specifically to the common gamma chain of a subfamily of cytokine receptors that includes IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Previous studies suggest that this tyrosine kinase plays key roles in mediating T cell functions, and inhibition of JAK3 has been shown to prevent graft rejection and decrease the severity of arthritis in rodent models. However, the functions of JAK3 in the development of skin immune responses and diseases such as psoriasis have not been determined. CD18 mutant PL/J mice develop spontaneous T cell-dependent psoriasiform skin disease with several similarities to human psoriasis. In this study, we treated mice with established skin disease with R348, a small molecule inhibitor of JAK3, and observed a marked attenuation of skin lesions following 6 wk of treatment. Histological analyses revealed major reductions of both epidermal and dermal lesion severity scores in R348-treated CD18-deficient PL/J mice compared with vehicle controls, which was associated with decreased CD4(+) T cell infiltration. In addition, systemic levels of IL-17, IL-22, IL-23, and TNF-alpha were significantly lower in mice receiving the compound, and T cells isolated from R348-treated mice also showed reduced phosphorylation of Stat5 after stimulation with IL-2. These findings suggest that small-molecule inhibitors of JAK3 may be useful in the treatment of inflammatory skin diseases such as psoriasis and strongly implicate JAK signaling events as important in the pathogenesis of this disease.
Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization (2005)

Forkhead box O (Foxo) transcription factors are emerging as critical transcriptional integrators among pathways regulating differentiation, proliferation, and survival, yet the role of the distinct Foxo family members in angiogenic activity of endothelial cells and postnatal vessel formation has not been studied. Here, we show that Foxo1 and Foxo3a are the most abundant Foxo isoforms in mature endothelial cells and that overexpression of constitutively active Foxo1 or Foxo3a, but not Foxo4, significantly inhibits endothelial cell migration and tube formation in vitro. Silencing of either Foxo1 or Foxo3a gene expression led to a profound increase in the migratory and sprout-forming capacity of endothelial cells. Gene expression profiling showed that Foxo1 and Foxo3a specifically regulate a nonredundant but overlapping set of angiogenesis- and vascular remodeling-related genes. Whereas angiopoietin 2 (Ang2) was exclusively regulated by Foxo1, eNOS, which is essential for postnatal neovascularization, was regulated by Foxo1 and Foxo3a. Consistent with these findings, constitutively active Foxo1 and Foxo3a repressed eNOS protein expression and bound to the eNOS promoter. In vivo, Foxo3a deficiency increased eNOS expression and enhanced postnatal vessel formation and maturation. Thus, our data suggest an important role for Foxo transcription factors in the regulation of vessel formation in the adult.
Safety and Biodistribution of an Equine Infectious Anemia Virus-Based Gene Therapy, RetinoStat ® , for Age-Related Macular Degeneration (2012)

RetinoStat(®) is an equine infectious anemia virus-based lentiviral gene therapy vector that expresses the angiostatic proteins endostatin and angiostatin that is delivered via a subretinal injection for the treatment of the wet form of age-related macular degeneration. We initiated 6-month safety and biodistribution studies in two species; rhesus macaques and Dutch belted rabbits. After subretinal administration of RetinoStat the level of human endostatin and angiostatin proteins in the vitreous of treated rabbit eyes peaked at ∼1 month after dosing and remained elevated for the duration of the study. Regular ocular examinations revealed a mild to moderate transient ocular inflammation that resolved within 1 month of dosing in both species. There were no significant long-term changes in the electroretinograms or intraocular pressure measurements in either rabbits or macaques postdosing compared with the baseline reading in RetinoStat-treated eyes. Histological evaluation did not reveal any structural changes in the eye although there was an infiltration of mononuclear cells in the vitreous, retina, and choroid. No antibodies to any of the RetinoStat vector components or the transgenes could be detected in the serum from either species, and biodistribution analysis demonstrated that the RetinoStat vector was maintained within the ocular compartment. In summary, these studies found RetinoStat to be well tolerated, localized, and capable of persistent expression after subretinal delivery.
Mechanical basis of cell shape: investigations with the scanning acoustic microscope (1995)

The shape of cells during interphase in sparse cultures often resembles that of fried eggs. XTH-2 cells, which have been derived from tadpole heart endothelia, provide a typical example of this type of shape. To understand the physical basis of this shape, the cytoskeleton of these cells has been investigated in detail. Subcellular elasticity data have been achieved by scanning acoustic microscopy (SAM). Their changes were observed during treatment of the cells with microtubule-disrupting agents (colcemid and low temperature), and shape generation in giant cells produced by electro-fusion was observed with SAM, revealing the role of the nucleus as a force centering organelle. From these observations combined with well-documented observations on cellular dynamics described in the literature, a model is developed explaining the fried-egg shape of cells by means of interacting forces and fluxes (cortical flow, bulk flow of cytoplasm, microtubule-mediated transport of cytoplasm) of cytoplasm. The model also allows the comprehension of the increase of tension in cells treated with colcemid.
Inhibiting the Cyclin-Dependent Kinase CDK5 Blocks Pancreatic Cancer Formation and Progression through the Suppression of Ras-Ral Signaling (2010)

Cyclin-dependent kinase 5 (CDK5), a neuronal kinase that functions in migration, has been found to be activated in some human cancers in which it has been implicated in promoting metastasis. In this study, we investigated the role of CDK5 in pancreatic cancers in which metastatic disease is most common at diagnosis. CDK5 was widely active in pancreatic cancer cells. Functional ablation significantly inhibited invasion, migration, and anchorage-independent growth in vitro, and orthotopic tumor formation and systemic metastases in vivo. CDK5 blockade resulted in the profound inhibition of Ras signaling through its critical effectors RalA and RalB. Conversely, restoring Ral function rescued the effects of CDK5 inhibition in pancreatic cancer cells. Our findings identify CDK5 as a pharmacologically tractable target to degrade Ras signaling in pancreatic cancer.
Bioactive Triterpene Saponins from the Roots of Phytolacca americana (2008)

Five new triterpene saponins named phytolaccasaponins N-1 (1), N-2 (2), N-3 (3) N-4 (4), and N-5 (5) were isolated from the roots of Phytolacca americana together with seven known triterpene saponins (6-12). The structures of the five new saponins were established as shown in structures 1-5 on the basis of their spectroscopic data. The MDR-reversal activity of 1-12 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780 AD cells in the presence of each compound. The most effective compound was 8 (155% of control at 25 microg/mL).
Arachidonate 5-Lipoxygenase Promoter Genotype, Dietary Arachidonic Acid, and Atherosclerosis (2003)

Variant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis. The observed diet-gene interactions further suggest that dietary n-6 polyunsaturated fatty acids promote, whereas marine n-3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.