gebhart/patrepeval huggingface dataset:
Chemopreventive effects of dietary folate on intestinal polyps in Apc+/-Msh2-/- mice. (2000)

Epidemiological and animal studies (reviewed in Y. I. Kim, J. Nutr. Biochemistry, 10: 66-88, 1999; J. B. Mason and T. Levesque, Oncology, 10: 1727-1743, 1996) suggest that dietary folate intake is inversely related to the risk of colorectal cancer. However, the optimal timing of folate intervention and mechanisms by which folate modulates colorectal carcinogenesis have not been clearly established. A recently developed murine model of intestinal tumorigenesis, which carries a heterozygous mutation in the Apc gene and a null mutation in the Msh2 gene (Apc+/-Msh2-/-), was used to determine the effect of dietary folate on intestinal tumorigenesis. Apc+/- Msh2-/- mice were randomized to receive either 0 or 8 mg of folate/kg diet starting at either 3 or 6 weeks of age. The 3- and 6-week diet starts represent intervention before and after the establishment of neoplastic foci, respectively. At 11 weeks of age, mice were killed, and the small intestines and colons were analyzed for adenomas and aberrant crypt foci (ACF). Serum folate concentrations were determined by a standard microbiological assay. Genomic DNA methylation was assessed by in vitro [3H]methyl incorporation into hepatic DNA and by a methyl-sensitive restriction digestion method. Microsatellite instability was determined in matched normal and polyp DNA from the small intestine and colon at 5 loci. Serum folate concentrations accurately reflected dietary folate levels (P < 0.005). Folate supplementation, started before the establishment of neoplastic foci, significantly decreased the number of small intestinal adenomas (by 2.7-fold; P = 0.004) and colonic ACF (by 2.8-fold; P = 0.028) and colonic adenomas (by 2.8-fold; P = 0.1) compared with a moderate degree of folate deficiency. In contrast, a moderately folate-deficient diet, started after the establishment of neoplastic foci, significantly reduced the number of small intestinal adenomas (by 4.2-fold; P = 0.001) but had no effect on colonic ACF and adenomas compared with folate supplementation. Genomic DNA methylation and microsatellite instability do not seem to play a major role in folate-modulated intestinal and colonic tumorigenesis in this model. In conclusion, in this murine model, dietary folate supplementation significantly protects against small intestinal and colorectal tumorigenesis if it is provided before the establishment of neoplastic foci However, if it is provided after the establishment of neoplastic foci, dietary folate seems to have an opposite effect. These data suggest that the timing of folate intervention is critical in providing an effective and safe chemopreventive effect on intestinal tumorigenesis. Notwithstanding the limitations associated with this model, our data suggest that the optimal timing of folate intervention must be established before folate supplementation can be used as a safe chemopreventive agent against colorectal cancer.
Therapeutic application of a radiolabelled monoclonal antibody in nude mice xenografted with human neuroblastoma: Tumoricidal effects and distribution studies (1985)

Monoclonal antibody UJ13A radiolabelled with isotopes of iodine has been shown to selectively localize to human neuroblastoma xenografts. When 131I-UJ13A conjugates were given to nude mice at high doses (100-150 microCi), tumours temporarily disappeared, only to regrow. No selection for neuroblastoma cells that were UJ13A - negative was observed. Distribution studies on mice receiving radiolabelled UJ13A demonstrated the antibody is rapidly lost from the blood of animals. This cannot be accounted for by selective uptake into xenografts or any other mouse organ examined. We concluded there is a rapid equilibration of isotope between intra- and extravascular spaces in the animal. The rapid, biphasic loss of UJ13A from the blood of mice may explain why so little injected antibody can target to the human tumour xenografts.
Human Steroid Biosynthesis for the Oncologist (2012)

In 2005, results from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial ushered in a new era of endocrine therapy for hormone-responsive malignancies. This study demonstrated that, compared with tamoxifen (a selective estrogen receptor modulator), anastrozole (aromatase inhibitor [AI]) prolonged time to recurrence and disease-free survival for postmenopausal women with breast cancer. The advantage was even greater for those with estrogen receptor-positive (ER) tumors, and anastrozole was better tolerated than tamoxifen. Since then, AIs have become first-line adjuvant therapy for ER breast cancer in postmenopausal women.In late 2010, a trial comparing abiraterone acetate (a 17-hydroxylase/17,20-lyase [CYP17A1] inhibitor) plus prednisone versus prednisone alone in men with castration-resistant prostate cancer (CRPC) previously treated with docetaxel chemotherapy was terminated early because of the survival benefit in the abiraterone acetate arm. This result not only validated a new therapy for CRPC but also, with the antecedent phase I-II abiraterone studies, shattered our understanding of the molecular mechanisms underpinning CRPC development and progression.Aromatase inhibitors and CYP17A1 inhibitors will be widely used by oncologists, yet fellowship programs provide little training in steroid biosynthesis, compared with training in the biology of standard chemotherapies. Consequently, these drugs might be used without an appreciation of their caveats and pitfalls. The purpose of this review was to acquaint practicing oncologists with the fundamental principles and pathways of steroid biosynthesis, to improve their understanding of how and why these drugs work, and to alert these physicians to potential problems related to the drugs' mechanisms of action.
Impact of Passive Tip-Injection on Tip-Leakage Flow in Axial Low Pressure Turbine Stage (2015)

In addition to geometrical modifications of the blade tip for reducing tip-leakage mass flow rate the method of passive tip-injection serves as an aerodynamic resistance towards the tip-leakage flow. The impact of this method has been investigated thoroughly at unshrouded blades in linear cascades. Furthermore combinations of shrouded blades with passive tip-injection have been investigated analytically as well as via numerical simulations for incompressible flow in linear cascades. The objective of this paper is to consider a real uncooled low pressure turbine stage with shrouded blades and to investigate the effect of passive tip-injection on various operational characteristics. CFD calculations have been carried out in a rotational frame taking into consideration compressible flow and serve for evaluating the method of passive tip-injection in the given turbine stage. Experimental data obtained from the machine without tip-injection serve as boundary conditions for the CFD calculations.
Two-dimensional model seismology (1954)

Abstract The solutions of many problems in seismology may be obtained by means of ultrasonic pulses propagating in small scale models. Thin sheets, serving as two dimensional models, are particularly advantageous because of their low cost, availability, ease of fabrication into various configurations, lower energy requirements, and appropriate dilatational-to-shear-velocity ratios. Four examples are presented: flexural waves in a sheet, Rayleigh waves in a low velocity layer overlying a semi-infinite high velocity layer, Rayleigh waves in a high velocity layer overlying a semi-infinite low velocity layer, and body and surface waves in a disk.
Functional interactions between papillomavirus E1 and E2 proteins (1997)

DNA replication of papillomaviruses requires the viral E1 and E2 proteins. These proteins bind cooperatively to the viral origin of replication (ori), which contains binding sites for both proteins, forming an E1-E2-ori complex which is essential for initiation of DNA replication. To map the domains in E2 that are involved in the interaction with E1, we have used chimeric bovine papillomavirus (BPV)/human papillomavirus type 11 (HPV-11) E2 proteins. The results from this study show that both the DNA binding domain and the transactivation domain from BPV E2 independently can interact with BPV E1. However, the roles of these two interactions are different: the interaction between E1 and the activation domain of E2 is necessary and sufficient for cooperativity in binding and for DNA replication; the interaction between E1 and the DNA binding domain of E2 is required only when the binding sites for E1 and E2 are adjacent to each other, and the function of this interaction appears to be to facilitate the interaction between E1 and the transactivation domain of E2. These results indicate that the cooperative binding of E1 and E2 to the BPV ori takes place via a novel two-stage mechanism where one interaction serves as a trigger for the formation of the second, productive, interaction between the two proteins.
Two-Dimensional, Model-Based, Boundary Matching Using Footprints (1986)

In this paper, we describe a technique for geometrically hash ing two-dimensional model objects. Used in conjunction with other methods for recognizing partially obscured and over lapping objects, this technique enables us to recognize over lapping, two-dimensional objects selected from large data bases of model objects without significant performance degradation when the database is enlarged. This technique is based on use of a synthetic attribute of an object, which we will call its footprint. Experimental results from databases of up to 100 objects are presented.
α-Difluoromethylornithine Induction of Apoptosis (2001)

α-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the first enzyme in polyamine synthesis. Previous work showed simultaneous administration of DFMO and a zinc-deficient (ZD) diet to weanling rats from the beginning inhibited the onset of zinc-deficiency-induced esophageal cell proliferation by activating apoptosis and reduced the incidence of N- nitrosomethylbenzylamine (NMBA)-induced esophageal cancer. Because esophageal cancer initiation by NMBA is very rapid in ZD rats, this study determined whether DFMO is effective in preventing esophageal carcinogenesis when administered after the establishment of a carcinogenic environment. Weanling rats were given a ZD diet for 5 weeks to establish sustained increased esophageal cell proliferation and then an intragastric dose of NMBA. Thereafter, 20 rats were switched to DFMO-containing water while nine control ZD animals remained on deionized water; all of the animals continued on the ZD diet. Esophagi were collected 15 weeks later. The upper portion was processed for immunohistochemical analysis of cell proliferation, apoptosis, and expression of related genes, and the lower was processed for polyamine content. DFMO substantially reduces the levels of esophageal putrescine and spermidine and esophageal tumor incidence from 89 to 10% in ZD rats. Importantly, DFMO-treated ZD esophagi display increased rate of apoptosis accompanied by intense bax expression and greatly reduced cell proliferation by proliferating cell nuclear antigen expression. In addition, the p16ink4a/retinoblastoma control at G1 to S, deregulated in ZD esophagi, is restored after DFMO treatment. These results demonstrate that DFMO, a highly effective chemopreventive agent in esophageal carcinogenesis, reverses and counteracts esophageal cell proliferation/cancer initiation in ZD animals by way of stimulating apoptosis.
Plasma-activated medium as adjuvant therapy for lung cancer with malignant pleural effusion (2020)

This study compared effects of plasma-activated medium (PAM) with effects of conventional clinical thermal therapy on both lung cancer cells and benign cells for management of malignant pleural effusion (MPE). For MPE treatment, chemotherapy, photodynamic therapy, and thermal therapy are used but caused systemic side effects, patient photosensitivity, and edema, respectively. Recent studies show that plasma induces apoptosis in cancer cells with minor effects on normal cells and is cost-effective. However, the effects of plasma on MPE have not been investigated previously. This study applied a nonthermal atmospheric-pressure plasma jet to treat RPMI medium to produce PAM, carefully controlled the long-life reactive oxygen and nitrogen species concentration in PAM, and treated the cells. The influence of PAM treatment on the microenvironment of cells was also checked. The results indicated that PAM selectively inhibited CL1-5 and A549 cells, exerting minor effects on benign mesothelial and fibroblast cells. In contrast to selective lethal effects of PAM, thermal therapy inhibited both CL1-5 and benign mesothelial cells. This study also found that fibroblast growth factor 1 is not the factor explaining why PAM can selectively inhibit CL1-5 cells. These results indicate that PAM is potentially a less-harmful and cost-effective adjuvant therapy for MPE.
Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies (2010)

The proposed measures reflect the most relevant morphological and clinical features of DCI without regard to pathogenesis to be used as an outcome measure in clinical trials and observational studies.
Development of an Activity‐Based Probe and In Silico Design Reveal Highly Selective Inhibitors for Diacylglycerol Lipase‐α in Brain (2013)

A model method: A strategy that combines a knowledge-based in silico design approach and the development of novel activity-based probes (ABPs) for the detection of endogenous diacylglycerol lipase-α (DAGL-α) is presented. This approach resulted in the rapid identification of new DAGL-α inhibitors with high selectivity in the brain proteome. ABPP=activity-based protein profiling.
Copper-zinc superoxide dismutase in Haemophilus species (1992)

Copper-zinc superoxide dismutases ([Cu,Zn]-SODs) are ubiquitous in eukaryotes but have rarely been found in prokaryotes. A gene for [Cu,Zn]-SOD (sodC) has recently been cloned from Haemophilus influenzae type b and H. parainfluenzae, so other Haemophilus and related species were screened for the presence of [Cu,Zn]-SODs by visualization of bands of SOD activity in non-denaturing polyacrylamide gels and by gene probing. Strains of H. aphrophilus, H. paraphrophilus, H. haemolyticus, H. paraphrohaemolyticus, some non-typable H. influenzae, H. haemoglobinophilus (canis) and H. parasuis were all found to have [Cu,Zn]-SOD activity (inhibited by 2 mM-cyanide) in polyacrylamide gels. In a Southern blot analysis, DNA from H. aphrophilus, H. paraphrophilus, H. haemolyticus and [Cu,Zn]-SOD-containing non-typable H. influenzae--but not the other species--hybridized to a 360 nucleotide DNA probe containing the 5'-part of sodC cloned from H. influenzae type b. Bacterial [Cu,Zn]-SODs are more prevalent than has previously been recognized.
Origin of Mammalian Gonadotropin-Releasing Hormones (1993)

GONADOTROPIN-releasing hormone (GnRH) plays a pivotal role in reproduction. The existence of this neuropeptide, also called LHRH, was predicted in the 1950s (1), but the structure of the 10 amino acid peptide for porcine and ovine brains was not reported until the 1970s (2, 3). In the 20 yr since then, only one form of GnRH has been identified in most placental mammals, and this is still considered to be the sole neuropeptide causing the release of LH and FSH. The structure and functions of the mammalian form of GnRH have been reviewed a number of times (4s–8). Meanwhile, both mammalian GnRH and related forms of GnRH are now known to be present in primitive placental mammals, nonplacental mammals, and other vertebrates. Novel functions, in addition to the release of gonadotropins, exist. Studies of GnRH peptides and their genes have altered our views on the origin, function, and regulation of this neuropeptide.
Anatomy of the cervical intervertebral foramina: vulnerable arteries and ischemic neurologic injuries after transforaminal epidural injections☆ (2005)

Cervical transforaminal epidural steroid injections are performed for the treatment of radicular pain. Multiple recent case reports have raised safety concerns regarding neurologic deficits such as anterior spinal artery syndrome and cerebellar injury after these injections. To investigate the potential causes of these injuries, an anatomic study was conducted. In this study of 10 embalmed cadavers, the cervical intervertebral foramina were examined to determine if the ascending or deep cervical arteries supplied radicular or segmental medullary arteries potentially susceptible to cannulation or needle trauma during transforaminal injection. In two specimens, dissection was carried down to the spinal cord, demonstrating the anterior spinal, radicular, and segmental medullary arteries. Of 95 intervertebral foramina dissected, 21 had an arterial vessel proximal to the posterior aspect of the foraminal opening. Seven of these 21 were spinal branches that entered the foramen posteriorly, potentially forming radicular or segmental medullary vessels to the spinal cord. One additional ascending cervical artery formed a segmental medullary artery that joined the anterior spinal artery. This would only be injured by anterior needle misplacement. Of the seven foraminal branches, three were included in the deep dissections. Two contributed to segmental medullary arteries and one to a radicular artery. Variable anastomoses between the vertebral and cervical arteries were found. Therefore, it is possible to introduce steroid particles into the vertebral circulation via the cervical arteries. Critical arteries are located in the posterior aspect of the intervertebral foramen and may be vulnerable to injection or injury during transforaminal epidural steroid injection.
HIGH PURITY URANIUM COMPOUNDS. Final Report (1961)

Uranium-aluminum compounds were prepared by solidsolid reaction of aluminum powder and uranium hydride; x-ray-diffraction patterns showed that single phases of UAl/sub 2/, UAl/sub 3/, and UAl/sub 4/ could be achieved. The uranium-beryllium compound, UBe/sub 1//sub 3/, was prepared by solid-solid reaction of berylllum powder and uranium hydride. The uranium-boron compounds, UB/sub 2/ UB/sub 4/, and UB/sub 1//sub 2/ were prepared by solid reaction, and single borides were obtained; carbon contamination was especially serious in these samples. The uranium-carbon compounds, UC and UC/sub 2/, were prepared by solid-solid reactlons to 1200 deg C; the x-ray-diffraction patterns showed a mixture of phases, and higher temperatures are probably required. The uranium- nitrogen compounds, UN and UN/sub 2/, were prepared by reaction of uranium with ammonia at 850 deg C for UN/sub 2/ and subsequent heating of that product in vacuum for UN. The uranium-selenium compounds, USe and USe/sub 2/, were prepared in very small samples; the violence of the reaction of selenium with uranium hydride and the lack of availability of hydrogen selenide limits the size of preparations. The uranium-silicon samples, USi/sub 2/ and USi/sub 3/ were prepared by solid-solid reaction of UH/sub 3/ and 8i; numerous attempts were made to prepare U8i. One of the USi/sub 2/ samples was alpha -USi/sub 2/ and the other was beta -USi/sub 2/. The uranium-sulfur compounds, US and US/sub 2/, were prepared; US/sub 2/ was prepared by forming unanium hydride in a flow furnace and then reacting the hydride with hydrogen sulfide; US was prepared by reacting some of the US/sub 2/ with UH/sub 3/. (auth)
Resistance and cross‐resistance to imidacloprid and thiamethoxam in the Colorado potato beetle <i>Leptinotarsa decemlineata</i> (2006)

One of the major challenges in managing the Colorado potato beetle, Leptinotarsa decemlineata (Say) is its remarkable ability to develop resistance to virtually every insecticide that has ever been used against it. Resistance is particularly common throughout northeastern USA as far north as Maine. The first instances of resistance to imidacloprid have already been reported from several locations in New York, Delaware and southern Maine. Rotating insecticides with different modes of action may delay insecticide resistance, but successful implementation of this technique depends on a good understanding of resistance and cross-resistance patterns in populations of target pests. LC(50) values were measured for imidacloprid and thiamethoxam in Colorado potato beetle populations from a variety of locations in the USA and Canada using diet incorporation bioassays. The field performance of imidacloprid, thiamethoxam and clothianidin against imidacloprid-resistant beetles on a commercial potato farm in southern Maine was also evaluated. Correlation between LC(50) values for imidacloprid and thiamethoxam was highly significant, even when populations previously exposed to thiamethoxam were excluded from the analysis. There was no statistically detectable difference in the LC(50) values between populations exposed to both insecticides and to imidacloprid alone. Applications of neonicotinoid insecticides at planting delayed build-up of imidacloprid-resistant beetle populations on field plots by 1-2 weeks but failed to provide adequate crop protection. Consistently with bioassay results, there was also substantial cross-resistance among the three tested neonicotinoid insecticides. Results of the present study support the recommendation to avoid rotating imidacloprid with thiamethoxam as a part of a resistance management plan.
Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers (2006)

In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke.
Diabetes augments and inhaled nitric oxide prevents the adverse hemodynamic effects of transfusing syngeneic stored blood in mice (2012)

Transfusion of syngeneic SRBCs or the supernatant from SRBCs produces systemic hypertension and vasoconstriction in db/db mice. It is likely that RBC storage, by causing in vitro hemolysis and posttransfusion hemoglobinemia, produces sustained NO scavenging and vasoconstriction in mice with endothelial dysfunction. Vasoconstriction is prevented by oxidizing the supernatant of SRBCs or breathing NO during SRBC transfusion.