gebhart/patrepeval huggingface dataset:
Abstract P3-14-09: Preclinical Safety and Activity of MM-302, a HER2-Targeted Liposomal Doxorubicin Designed To Have an Improved Safety and Efficacy Profile over Approved Anthracyclines (2010)

Abstract Background: Anthracyclines have been an effective backbone of breast cancer therapies for decades. However, cardiotoxicity issues associated with free anthracyclines have limited their effective use in the clinic and ledto the exploration of anthracycline-free regimens, particularly with HER2- positive cancers that require treatment with another cardiotoxic agent, trastuzumab. While liposomal doxorubicin formulations have succeeded in reducing cardiotoxicity, they have failed to demonstrate clearcut efficacy advantages and can involve other toxicities. To address the safety and efficacy limitations of currently available anthracyclines, we have designed a new liposomal formulation, MM-302, that targets doxorubicin to HER2- overexpressing tumor cells. Antibody fragments that bind to HER2 without blocking HER2-mediated signaling are coupled to the outer surface of pegylated liposomal doxorubicin. MM-302 specifically binds and enters tumor cells overexpressing HER2 with minimal uptake into normal cells such as cardiomyocytes which express low levels of HER2. Materials and methods: MM-302, untargeted pegylated liposomal doxorubicin (PLD), and free doxorubicin were compared for their uptake into target and nontarget cells, pharmacokinetics, biodistribution, tumor microdistribution using FACS and confocal microscopy, and anti-tumor activity in BT-474 and NCI-N87 xenograft models. Results: Cellular uptake studies in tumor cell lines expressing various levels of HER2 demonstrate that MM-302 delivers significantly higher doxorubicin levels to HER2 over-expressing tumor cells compared to PLD as well as similar or higher levels than highly permeable free doxorubicin. However, in human cardiomyocytes, while free doxorubicin was again taken up at high levels, doxorubicin uptake was dramatically lower with both MM-302 and PLD. Pharmacokinetic studies in mice demonstrate that MM-302 has a similar half life, clearance, and organ distribution compared to PLD. In HER2-overexpressing BT-474 breast and NCI-N87 gastric tumor xenografts, MM-302 exhibits superior anti-tumor activity to both free anthracyclines and PLD. Tumor microdistribution studies further suggest that differences in the localization of doxorubicin in the tumor may be responsible for the enhanced activity of MM-302 compared to free doxorubicin and PLD. Discussion: These preclinical data suggest that MM-302 may provide in clinical practice a new opportunity to specifically deliver an anthracycline to HER2-overexpressing tumors with a potentially cleaner safety profile and improved efficacy over currently available free or liposomal doxorubicin. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-09.
Antifertility Properties of Prostaglandin F2α (1969)

The effect of prostaglandin F2α (PGF2α) on pregnancy in the rat and rabbit has been studied. PGF2α was found to be 100% effective in preventing or terminating pregnancy in the rat when administered subcutaneously at a dose of 2 mg/day over any consecutive 3-day period from Day 4 through Day 13 after coitus. On Day 4 through Day 6 of pregnancy the minimal effective dose to achieve these results was 3.2 mg/kg/day (a total dose of 9.6 mg/kg). Orally administered PGF2α at a 10 fold increase in dosage was ineffective in interrupting pregnancy. Prostaglandin F1α was 100% active in rats at a subcutaneous dose approximately 10 fold above that of F2α. Exogenous progestogen was effective in maintaining pregnancy in rats that had received more than two times the MED100 dose of prostaglandin F2α. Ergocornine (2 mg/day) inhibited lactation and retarded growth of neonatal offspring while PGF2α was without effect on lactation. In the rabbit PGF2α was 100% effective in blocking nidation when administered by subcutaneous injection at a dose of 5 mg/kg/day on Days 4 through 8 of pregnancy.
Laser acceleration of electrons in vacuum (1995)

Several features of vacuum laser acceleration are reviewed, analyzed, and discussed, including electron acceleration by two crossed laser beams and acceleration by a higher-order Gaussian beam. In addition, the vacuum beat wave accelerator (VBWA) concept is proposed and analyzed. It is shown that acceleration by two crossed beams is correctly described by the Lawson-Woodward (LW) theorem, i.e., no net energy gain results for a relativistic electron interacting with the laser fields over an infinite interaction distance. Finite net energy gains can be obtained by placing optical components near the laser focus to limit the interaction region. The specific case of a higher-order Gaussian beam reflected by a mirror placed near focus is analyzed in detail. It is shown that the damage threshold of the mirror is severely limiting, i.e., substantial energy gains require very high electron injection energies. The VBWA, which uses two copropagating laser beams of different frequencies, relies on nonlinear ponderomotive forces, thus violating the assumptions of the LW theorem. Single-particle simulations confirm that substantial energy gains are possible and that optical components are not needed near the focal region.
The treatment of bullous pemphigoid with tetracycline and niacinamide. A preliminary report (1986)

• Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease. (<i>Arch Dermatol</i>1986;122:670-674)
Biomimetic, bioactive etheric polyphosphazene‐poly(lactide‐<i>co</i>‐glycolide) blends for bone tissue engineering (2009)

The long-term goal of this work is to develop biomimetic polymer-based systems for bone regeneration that both allow for neutral pH degradation products and have the ability to nucleate bonelike apatite. In this study, the etheric biodegradable polyphosphazene, poly[(50%ethyl glycinato)(50%methoxyethoxyethoxy)phosphazene] (PNEG(50)MEEP(50)) was blended with poly(lactide-co-glycolide) PLAGA and studied their ability to produce high-strength degradable biomaterials with bioactivity. Accordingly, two blends with weight ratios of PNEG(50)MEEP(50) to PLAGA 25:75 (BLEND25) and 50:50 (BLEND50) were fabricated using a mutual solvent approach. Increases in PNEG(50)MEEP(50) content in the blend system resulted in decreased elastic modulus of 779 MPa when compared with 1684 MPa (PLAGA) as well as tensile strength 7.9 MPa when compared with 25.7 MPa (PLAGA). However, the higher PNEG(50)MEEP(50) content in the blend system resulted in higher Ca/P atomic ratio of the apatite layer 1.35 (BLEND50) when compared with 0.69 (BLEND25) indicating improved biomimicry. Furthermore, these blends supported primary rat osteoblast adhesion and proliferation with an enhanced phenotypic expression when compared with PLAGA. These findings establish the suitability of PNEG(50)MEEP(50)-PLAGA biodegradable blends as promising bioactive materials for orthopedic applications.
Leaf growth rate per unit thermal time follows QTL‐dependent daily patterns in hundreds of maize lines under naturally fluctuating conditions (2006)

We have analysed daily patterns of leaf elongation rate (LER) in large data sets with 318 genotypes placed in naturally fluctuating temperature and evaporative demand, and examined the effect of targeted alleles on these patterns. The method consisted, firstly, in expressing elongation rate per unit thermal time, so it became temperature independent; secondly, in a joint analysis of diurnal fluctuations of elongation rate and of micrometeorological conditions in several experiments, and finally, in a comparison of daily patterns between groups of genotypes possessing targeted alleles. (1) Conditions for using thermal time at a time step of 15 min were first tested successfully in 318 recombinant inbred lines (RILs) of three mapping populations. (2) An analysis of 1989 time courses revealed a robust daily pattern of LER per unit thermal time (LERth) over several experiments. LERth was constant during the night and was reproducible (for a given RIL) over up to 10 consecutive nights in different experiments. It declined rapidly during the early morning, closely following the daily pattern of transpiration rate. (3) Groups of RILs carrying alleles conferring a high response to temperature had markedly higher night-time plateau of LER than those with low responses. Groups of RILs with high response to evaporative demand had rapid decreases in elongation rate at the transition between night and day, while this decrease was slower in groups of RILs with low response. These results open the way for using kinetics of responses to environmental stimuli as a phenotyping tool in genetic analyses.
Evaluation of MP-SoC interconnect architectures: a case study (2004)

Multiprocessor (MP-SoC) platforms are emerging as the latest trend in SoC design. These MP-SoCs consist of a large number of IP blocks in the form of functionally heterogeneous embedded processors. In this design paradigm, IP blocks need to be integrated using a structured interconnect template, for example, according to high-performance parallel computing architectures. A formal evaluation process is required before adopting a specific parallel architecture to SoC domain. Here, we propose an evaluation methodology based on performance metrics that include latency, throughput and silicon area requirements. As a case study, we present the results of such an evaluation for two MP-SoC interconnect topologies, i.e., the mesh and the butterfly fat-tree (BFT). This evaluation methodology can be extended to any other SoC interconnect topology without loss of generality.
Growth Hormone and Pituitary Radiotherapy, But Not Serum Insulin-Like Growth Factor-I Concentrations, Predict Excess Mortality in Patients with Acromegaly (2004)

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF-I remain uncertain. The West Midlands Pituitary database contains details of 419 patients (241 female) with acromegaly. Serum IGF-I data from the Regional Endocrine Laboratory were available for 360 patients (86%). At diagnosis, mean age was 47 yr (range, 12-84) and mean duration of follow-up was 13 yr (0.5-48). Sixty-one percent were treated by surgery and 39% by nonsurgical means. Radiotherapy was used alone or as adjuvant therapy in 50%. All patients were registered with the Office of National Statistics to obtain information on deaths. At the date of analysis (31 December 2001), 95 of the 419 patients had died (43 males), giving a standardized mortality ratio of 1.26 [confidence interval (CI), 1.03-1.54; P = 0.046]. After controlling for age and sex, data indicated that mortality was increased in subjects with posttreatment GH levels more than 2 micro g/liter, compared with those with levels less than 2 micro g/liter [ratio of mortality rates (RR), 1.55 (range, 0.97-2.50); P = 0.068]. By contrast, a much smaller increase was observed for subjects with elevated posttreatment IGF-I levels compared with those with normal levels [RR, 1.20 (range, 0.71-2.03); P = 0.50]. Treatment with radiotherapy was associated with increased mortality [RR, 1.67 (range, 1.09-2.56); P = 0.018], with cerebrovascular disease the predominant cause of death [standardized mortality ratio, 4.42 (range, 2.71-7.22); P = 0.005]. These results confirm the increased mortality in acromegaly and suggest that reduction of GH levels to less than 2 micro g/liter is beneficial in terms of improving long-term outcome. The sole use of IGF-I as a marker for effective treatment of acromegaly is not justified by this data. This study also highlights the potential deleterious effect of radiotherapy.
Low-threshold diode-pumped dye laser (1994)

A cw dye laser pumped by laser diodes has been demonstrated. Two 10 mW visible laser diodes were polarization combined to pump a rhodamine 700 dye jet laser. The absorbed pump threshold power was 5.6 mW and 0.28 mW of output power was produced at 758 nm. The resonator was scalable and generated over 360 mW with a slope efficiency of 57% when pumped with a DCM dye laser at 660 nm.
Stacked Device of Polymer Light-Emitting Diode Driven by Metal-Base Organic Transistor (2008)

We fabricated a new light-emitting device that combined a polymer light-emitting diode (PLED) and a vertical-type metal-base organic transistor (MBOT) through a floating electrode. By employing a layered floating electrode of Mg:Ag/Au, the MBOT on the PLED was operated successfully and a current amplification factor of approximately 20 was observed. The PLED luminescence exceeding 100 cd/m2 can be modulated using the MBOT with a low base voltage (2.8 V) and VCC (8 V). The emission contrast (on/off ratio) was improved with insertion of an insulating layer under the base, and the cut-off frequency was estimated to be 8 kHz. This device is expected to be a promising driving system of organic light-emitting diode (OLED), realizing low voltage and high numerical aperture.
Assessing Multiple Resolution Scales in History Matching With Metamodels (2007)

Abstract In this paper we present a new multiscale approach to history matching assisted by a neural network metamodel. The method starts with the construction of a fine scale a priori model that includes geological and geostatistical information. We then apply a singular value decomposition (SVD) in order to obtain a parametric representation of the permeability field, in a way that a fixed set of eigenimages are determined with the parameters to be inverted as weights in the expansion. Through this procedure not only is the number of parameters significantly reduced, but also the weights in the SVD expansion define a hierarchy that naturally separates the different resolution scales in the system. We show that the multiscale procedure alone helps to significantly reduce the CPU time required to accomplish the parameter estimation. Furthermore, the reduced parameter space facilitated the training of the neural network engine.
Nonalcoholic Steatohepatitis: Definition and Pathology (2001)

Nonalcoholic steatohepatitis (NASH) is a significant form of chronic liver disease in adults and children. The natural history of NASH ranges from indolent to end-stage liver disease. Current studies are focusing on identification of histologic and/or clinical markers of progression. NASH may be an underlying cause of cryptogenic cirrhosis, and the lesions of NASH may recur in allograft livers. An expanding array of clinical conditions and pathogenetic mechanisms have been identified, but many cases remain "idiopathic"; lack of significant alcohol use is, by definition, common to all cases. Neither clinical evaluation nor laboratory values can ensure either the diagnosis or the exclusion of NASH, and liver biopsy interpretation continues to be considered the "gold standard" for diagnosis. The lesions in NASH are similar but not identical to those of alcoholic steatohepatitis; exact, specific histologic criteria for the diagnosis are currently under discussion. The lesions most commonly accepted for NASH include steatosis, hepatocyte ballooning degeneration, mild diffuse lobular mixed acute and chronic inflammation, and perivenular, perisinusoidal collagen deposition. Zone 3 accentuation may be detected. Mallory's hyaline, vacuolated nuclei in periportal hepatocytes, lobular lipogranulomas, and PAS-diastase-resistant Kupffer cells are common. In biopsy specimens from children, portal inflammation may be more prominent than in adults. Progression of fibrosis may result in bridging septa and cirrhosis. The lesions of steatohepatitis may be noted concurrently with other forms of chronic liver disease. A histological "grading and staging" system has been developed to reflect the unique features of steatohepatitis, gradations of severity and fibrosis, and to promote uniform reporting of the histopathology.
PYRROLE CHEMISTRY: V. FRIEDEL–CRAFTS ISOPROPYLATIONS OF SOME PYRROLE DERIVATIVES (1966)

The Friedel–Crafts isopropylations of methyl 2-pyrrolecarboxylate, 2-pyrrolecarboxaldehyde, and 2-pyrryl methyl ketone have been investigated under a variety of conditions. Products have been isolated and identified. The effects of different Lewis acid catalysts, solvents, and reaction times upon conversion and product isomer distribution have been determined. These results support the sequence of mechanistic steps suggested in an earlier publication. Further experiments have involved attempted rearrangements and disproportionations under alkylation conditions. The evidence indicates that Lewis acid complexing of the carbonyl oxygen deactivates position 4 in electrophilic substitution less than it does positions 3 and 5. The extent of deactivation of the different positions varies from 2-ester to 2-ketone to 2-aldehyde. Some proton nuclear magnetic resonance investigations of the Lewis acid complexes of these 2-carbonyl pyrroles are also reported.
Replacement of benzidine by copper ethylacetoacetate and tetra base as spot-test reagent for hydrogen cyanide and cyanogen (1966)

F. Feigl and V. Anger, Analyst, 1966, 91, 282 DOI: 10.1039/AN9669100282
Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice (1998)

To study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST-deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.
Pinitol from Sugar Pine Stump Wood (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPinitol from Sugar Pine Stump WoodArthur B. AndersonCite this: Ind. Eng. Chem. 1953, 45, 3, 593–596Publication Date (Print):March 1, 1953Publication History Published online1 May 2002Published inissue 1 March 1953https://pubs.acs.org/doi/10.1021/ie50519a037https://doi.org/10.1021/ie50519a037research-articleACS PublicationsRequest reuse permissionsArticle Views91Altmetric-Citations28LEARN 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 options Get e-Alerts
Asymmetric transformation of a racemic α‐(phthalimidooxy)arylacetic ester by a combination of preferential crystallization and simultaneous racemization (1993)

Abstract An asymmetric transformation of racemic t ‐butyl 2‐(3,4‐ O ‐carbonyldioxy‐phenyl)‐2‐(phthalimidooxy)acetate [(RS)‐ 2b ] into one of its optically active forms was carried out by a combination of preferential crystallization of a desired enantiomer and the simultaneous racemization of the antipode. (R)‐ 2b was easily racemized in diethylketone in the presence of a small amount of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). Under the conditions for racemization, the asymmetric transformation was achieved successfully to give (S)‐ 2b with 84% optical purity in 80% yield. A potent antipseudomonal cephalosporin M‐14659 ( 1 ) was prepared from the pure (S)‐ 2b which was obtained by the recrystallization of the crude (S)‐ 2b . © 1993 Wiley‐Liss, Inc.
Antigenic cross-reactions between fimbriae expressed by<i>Salmonella enteritidis, S. dublin</i>and an 18 kDa outer membrane associated protein expressed by<i>Escherichia coli</i>O126: H27 (1994)

A commercial kit (SEFEX), designed to detect strains of Salmonella enteritidis, was used to demonstrate antigenic cross-reactions between the fimbriae of S. enteritidis and an 18 kDa outer membrane protein expressed by enteroaggregative strains of E. coli O126: H27.
Hydrogenation of CO<sub>2</sub> to Methanol on CeO<sub><i>x</i></sub>/Cu(111) and ZnO/Cu(111) Catalysts: Role of the Metal–Oxide Interface and Importance of Ce<sup>3+</sup> Sites (2016)

The role of the interface between a metal and oxide (CeOx–Cu and ZnO–Cu) is critical to the production of methanol through the hydrogenation of CO2 (CO2 + 3H2 → CH3OH + H2O). The deposition of nanoparticles of CeOx or ZnO on Cu(111), θoxi < 0.3 monolayer, produces highly active catalysts for methanol synthesis. The catalytic activity of these systems increases in the sequence: Cu(111) < ZnO/Cu(111) < CeOx/Cu(111). The apparent activation energy for the CO2 → CH3OH conversion decreases from 25 kcal/mol on Cu(111) to 16 kcal/mol on ZnO/Cu(111) and 13 kcal/mol on CeOx/Cu(111). The surface chemistry of the highly active CeOx–Cu(111) interface was investigated using ambient pressure X-ray photoemission spectroscopy (AP-XPS) and infrared reflection absorption spectroscopy (AP-IRRAS). Both techniques point to the formation of formates (HCOO–) and carboxylates (CO2δ−) during the reaction. Our results show an active state of the catalyst rich in Ce3+ sites which stabilize a CO2δ− species that is an essential intermediate for the production of methanol. The inverse oxide/metal configuration favors strong metal–oxide interactions and makes possible reaction channels not seen in conventional metal/oxide catalysts.
In Vitro Migration Assays of Neural Stem Cells (2008)

We describe three rapid procedures for the in vitro investigation of molecular factors influencing the migration of neural precursors derived from embryonic or postnatal neural stem cells. In the first assay, factors influencing chain migration from the anterior subventricular zone of perinatal mice can be analyzed after explantation and embedding in Matrigel, a three-dimensional substrate mimicking the in vivo extracellular matrix. The second assay enables to assess soluble factors influencing radial migration away from adherent neurospheres in which embryonic stem cells have been expanded. In this example, neurospheres have been derived from the striatum primordium of embryonic mice. Finally, the directed migration of these precursor cells can be analyzed using a chemotaxis chamber assay, in which the directional movement (chemotaxis) of cells across a membrane occurs in controlled conditions. These three assays are useful tools to evaluate the importance of surface molecules and environmental factors, such as the polysialylated form of neural cell adhesion molecule (NCAM) or chemokines such as CXCL12, in the directional migration of neural precursors.