gebhart/patrepeval huggingface dataset:
Accurate dosimetry in 131I radionuclide therapy using patient-specific, 3-dimensional methods for SPECT reconstruction and absorbed dose calculation. (2005)

For target sizes down to 16 mL, highly accurate and precise dosimetry can be obtained with 3D methods for SPECT reconstruction and absorbed dose estimation. In the future, these methods can be applied to patients to potentially establish correlations between tumor regression and the absorbed dose statistics from 3D dosimetry.
Gene Expression Profiling of Breast, Prostate, and Glioma Cells following Single versus Fractionated Doses of Radiation (2007)

Studies were conducted to determine whether gene expression profiles following a single dose of radiation would yield equivalent profiles following fractionated radiation in different tumor cell lines. MCF7 (breast), DU145 (prostate), and SF539 (gliosarcoma) cells were exposed to a total radiation dose of 10 Gy administered as a single dose (SD) or by daily multifractions (MF) of 5 x 2 Gy. Following radiation treatment, mRNA was isolated at 1, 4, 10, and 24 h and processed for cDNA microarray analysis. To determine the influence of the tumor microenvironment on gene expression, one cell type (DU145) was evaluated growing as a solid tumor in athymic nude mice for both radiation protocols. Unsupervised hierarchical cluster map analysis showed significant differences in gene expression profiles between SD and MF treatments for cells treated in vitro, with MF yielding a more robust induction compared with SD. Several genes were uniquely up-regulated by MF treatment, including multiple IFN-related genes (STAT1, G1P2, OAS1, OAS3, G1P3, IFITM1) and TGF-beta-associated genes (EGR1, VEGF, THBS1, and TGFB2). DU145 cells grown in vivo exhibited a completely different set of genes induced by both SD and MF compared with the same cells exposed in vitro. The results of the study clearly show distinct differences in the molecular response of cells between SD and MF radiation exposures and show that the tumor microenvironment can significantly influence the pattern of gene expression after radiation exposures.
A study on the effect of agitation speeds for the optimization of manufacturing process of autonomic microcapsules (2006)

교반기 내에서의 교반속도 변화에 따라 제조된 자가치료용 마이크로캡슐의 물리적 특성을 입도분석기와 광학현미경을 통해 실험적으로 관찰하였다. 또한 자가치료용 마이크로캡슐의 제조공정을 이해하기 위해 3차원 수치해석의 수행을 통해 교반기 내에서의 유동 특성을 조사하였다. 연구결과에 따르면, 교반기 내에서의 교반속도는 마이크로캡슐의 크기를 결정하는 주요 인자임을 확인하였다. 액체가 혼합된 교반기 내에서는 회전하는 임펠러에 의해 제트와 끝단 와류 성분이 발생하였으며 임펠러의 블레이드 주위에 형성되는 와도는 교반속도가 높아질 때 증가함을 알 수 있었다. 또한 자가치료용 마이크로캡슐의 크기는 끝단 와류와 같은 작은 크기의 혼합 패턴 유동에 큰 영향을 받았다. The physical characteristics of autonomic microcapsules manufactured with various agitation speeds in a stirred tank were observed experimentally by a particle size analyzer and an optical microscope. The flow characteristics in a stirred tank were also investigated through a 3-dimensional numerical simulation to understand the manufacturing process of autonomic microcapsules. According to the results, we found that the agitation speed was the important factor to determine the sizes of microcapsules. The impeller-induced flow allowed the jet and tip-vortex pair components in the mixed fluid of a stirred tank. The vorticity around the blades in the impeller was increased as increasing the agitation speed. In addition, the size of autonomic microcapsules was strongly affected on the small scale mixing pattern such as a tip-vortex pair.
In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications (1998)

LPAS
Site‐specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening (1999)

Telomere shortening during human aging has been reported to be accelerated by oxidative stress. We investigated the mechanism of telomere shortening by oxidative stress. H2O2 plus Cu(II) caused predominant DNA damage at the 5' site of 5'-GGG-3' in the telomere sequence. Furthermore, H2O2 plus Cu(II) induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in telomere sequences more efficiently than that in non-telomere sequences. NO plus O2- efficiently caused base alteration at the 5' site of 5'-GGG-3' in the telomere sequence. It is concluded that the site-specific DNA damage at the GGG sequence by oxidative stress may play an important role in increasing the rate of telomere shortening with aging.
trp repressor/trp operator interaction. Equilibrium and kinetic analysis of complex formation and stability. (1992)

The trp repressor of Escherichia coli regulates transcription initiation in the trp operon by binding at an operator located within the trp promoter region. We have used a filter binding assay to analyze the interaction between purified trp repressor and a synthetic 43-base pair DNA fragment containing the natural trp promoter-operator region. In equilibrium binding experiments, the KD of high affinity binding of trp repressor to this DNA fragment was determined to be 2 x 10(-10) M. Low affinity binding was observed at repressor concentrations above 10 nM. In kinetic experiments with various input ratios of repressor to operator, trp repressor-operator complexes dissociated with equivalent, first-order kinetics. Instantaneous reduction of the tryptophan concentration resulted in increased rates of complex dissociation, indicating that loss of one or both tryptophan molecules from the repressor-operator complex destabilizes the complex. A heterodimeric repressor with a single tryptophan binding site was constructed and its affinity for operator was compared with that of ligand free aporepressor and tryptophan saturated repressor. The heterodimeric repressor had a 20-25-fold higher affinity for operator than did the aporepressor, and it had a 20-25-fold lower affinity for operator than did the tryptophan-saturated repressor.
Purification and Characterization of Human Chitotriosidase, a Novel Member of the Chitinase Family of Proteins (1995)

Recently we noted (Hollak, C.E.M., van Weely, S., van Oers, M.H.J., and Aerts, J.M.F.G. (1994) J. Clin. Invest. 93, 1288-1292) that the clinical manifestation of Gaucher disease is associated with a several hundred-fold increase in chitotriosidase activity in plasma. We report on the purification and characterization of the protein. Two major isoforms of chitotriosidase with isoelectric points of 7.2 and 8.0 and molecular masses of 50 and 39 kDa, respectively, were purified from the spleen of a Gaucher patient. The N-terminal amino acid sequence of the two forms proved to be identical. An antiserum raised against the purified 39-kDa chitotriosidase precipitated all isozymes. Chitotriosidase activity was earlier found to be completely absent in some individuals. These findings in combination suggest that a single gene may encode the different isoforms of chitotriosidase. Both the N-terminal sequence and an internal sequence chitotriosidase proved to be homologous to sequences in proteins that are members of the chitinase family (Hakala, B.E., White,C., and Recklies, A.D. (1993) J. Biol. Chem. 268, 25803-25810). The human chitotriosidase described here showed chitinolytic activity toward artificial substrates as well as chitin and may therefore be considered to be a chitinase.
Arterial Gene Transfer for Therapeutic Angiogenesis in Patients with Peripheral Artery Disease. St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts (1996)

The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease (PAD) include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients. The purpose of this clinical protocol is to document the safety of therapeutic angiogenesis achieved in this case by percutaneous catheter-based delivery of the gene encoding vascular endothelial growth factor (VEGF) in patients with PAD; and, as secondary objectives, investigate the bioactivity of this strategy to relieve rest pain and heal ischemic ulcers of the lower extremities. The rationale for this human protocol is based upon preclinical studies performed in a rabbit model of hindlimb ischemia. These studies are described in detail below and in the manuscripts enclosed in the Appendix to this proposal. In brief, a single intra-arterial bolus of VEGF recombinant human protein, delivered percutaneously to the ischemic limb via an intravascular catheter, resulted in angiographic, hemodynamic, physiologic, and histologic evidence of augmented collateral artery development. Subsequently, similar results were achieved using an angioplasty catheter with a hydrogel-coated balloon to deliver 400 micrograms of a plasmid containing the cDNA for VEGF to the internal iliac artery in the same animal model. Accordingly, we propose to administer arterial gene (VEGF) therapy to patients with rest pain and/or ischemic leg ulcers considered not to be candidates for conventional revascularization techniques. The dose of plasmid to be administered will be progressively escalated beginning with 500 micrograms for the first four patients, 1000 micrograms for the following six patients, 2000 micrograms for the third group of six patients, and 400 micrograms for the fourth group of six patients.
Formula-feeding reduces lactose digestive capacity in neonatal pigs (2006)

The intestine of newborn pigs develops rapidly during the first days postpartum. We investigated if feeding milk replacer (infant formula) as an alternative to colostrum has compromising effects on nutrient digestive function in the neonatal period. Nineteen piglets born at term were assigned to one of four treatments: (1) newborn controls; (2) natural suckling for 24 h; (3) tube-fed formula for 24 h; (4) tube-fed porcine colostrum for 24 h. All three fed groups showed significant increases in small-intestinal and colonic weights, villous heights and widths, maltase and aminopeptidase A activities, and decreases in dipeptidylpeptidase IV activity, relative to newborn pigs. Following oral boluses of mannitol, lactose or galactose, formula-fed pigs showed significantly reduced plasma levels of mannitol and galactose compared with colostrum-fed pigs. Activity of intestinal inducible NO synthase and plasma levels of cortisol were significantly increased, whereas intestinal constitutive NO synthase and alpha-tocopherol were decreased in formula-fed pigs compared with colostrum-fed pigs. Although formula-fed pigs only showed minor clinical signs of intestinal dysfunction and showed similar intestinal trophic responses just after birth, as those fed colostrum, lactose digestive capacity was markedly reduced. We conclude that formula-feeding may exert detrimental effects on intestinal function in neonates. Formula-induced subclinical malfunction of the gut in pigs born at term was associated with altered NO synthase activity and antioxidative capacity.
High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. (1993)

High-dose consolidation with CPA/cDDP/BCNU and ABMS after standard-dose CAF results in a decreased frequency of relapse in patients with high-risk primary breast cancer compared with historical series at the median follow-up of 2.5 years. Evaluation in a prospective, randomized trial is warranted and currently underway.
The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases. (1990)

We have previously described partial genomic sequences of arg, a human gene related to c-abl, and shown that it is expressed as a 12-kilobase transcript and is located at chromosome position 1q24-25. In this study we elucidate the complete coding sequence of arg by characterization of cDNA clones. Analysis of the predicted amino acid sequence of arg revealed that it is indeed closely related to that of c-abl. The two proteins are strikingly similar with regard to overall structural architecture as well as the amino acid sequences of their tyrosine kinase and src homologous 2 and 3 domains. In addition, arg, like c-abl, is expressed as two transcripts that result from a process of alternative splicing and encode alternative protein forms that differ only in their amino termini. The two genes define the Abelson subfamily of cytoplasmic tyrosine kinases and share a common homolog in Drosophila.
Validation of the selected dose of aflibercept (VEGF Trap) plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in a phase I clinical trial of patients (pts) with advanced solid tumors (STs): Preliminary results (2008)

14540 Background: Aflibercept (AF), a potent angiogenesis inhibitor fusion protein, is comprised of human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (Flk-1) extracellular domains fused to the Fc portion of human IgG1. A phase I dose escalation study established the AF 4.0 mg/kg + I-LV5FU2 (standard dose) every 2 weeks (q2w) as the recommended dose to be confirmed in a feasibility study. Methods: This was a randomized, double blind feasibility study of AF (4.0 mg/kg) or placebo + I-LV5FU2 at cycle 1, followed in subsequent cy by AF (4.0 mg/kg) + I-LV5FU2 q2w in pts with solid tumors. Study endpoints were to confirm the AF dose, explore the safety, preliminary efficacy and antivascular activity (DCE MRI) of AF. DCE MRI was performed at cycle 1 and 2, all imagings were centrally reviewed. Results: 27 pts were treated in both arms (15 male/12 female), median age 54 [39–75], ECOG PS 0/1/2: 12/11/4, with 70% of colorectal cancers. All pts received prior chemotherapy (CT): median 3 [1–6], 21 pts were previously treated with an I-based regimen. Pts received a total of 205 (median 8 [1–18]) treatment cycles and the AF relative dose intensity was 92%. The main grade (Gr) 3–4 AF-related toxicity (% pts) was hypertension (HTN) (15%). Moderate (Gr2) HTN (26%), dysphonia (11%), epistaxis (4%) and proteinuria (4%) were observed. No Gr 4 was reported. One pt (colon cancer previously exposed to I-based CT) achieved partial response and 21 pts had stable disease. Conclusions: AF 4.0 mg/kg is safely combined with I-LV5FU2 and is the recommended dose for phase III trials. Signs of activity are reported. Updated safety and efficacy results from this ongoing study will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Bring your own device (BYOD) with Cloud 4 education (2012)

This paper presents an outline of the issues encountered in the progression from wired PCs to supporting Bring Your Own Device (BYOD) for learners. The paper also documents the simultaneous transition to cloud hosting of teaching resources. The paper describes the issues that Letterkenny Institute of Technology faced in the planning and evaluation phase during the move to BYOD. It is expected that the details provided here will be of benefit to other educational institutions considering such a move
Inhibitory Effects of Triphosphate Derivatives of Oxetanocin G and Related Compounds on Eukaryotic and Viral DNA Polymerases and Human Immunodeficiency Virus Reverse Transcriptase (1992)

In order to clarify the biological activities of (-)-oxetanocin G, and (-)-oxetanocin A and its carbocyclic analogue, (-)-carboxetanocin G, the inhibitory effects of triphosphate derivatives of these compounds (OXT-GTP, OXT-ATP, and C-OXT-GTP) on eukaryotic and viral DNA polymerases were examined. DNA polymerase alpha purified from calf thymus was weakly inhibited by OXT-GTP and OXT-ATP but strongly by C-OXT-GTP, the Ki value being 0.22 microM. On the other hand, rat DNA polymerase beta was not affected by these analogues. DNA polymerase gamma purified from bovine testes was very weakly inhibited by OXT-GTP and OXT-ATP, but not by C-OXT-GTP. DNA polymerase from herpes simplex virus type-II (HSV-II) was strongly inhibited by all three analogues, the Ki values ranging from 0.5 to 1.0 microM. Human immunodeficiency virus-encoded reverse transcriptase (HIV RT) was also strongly inhibited by these three analogues, the Ki value of C-OXT-GTP being slightly smaller than that of OXT-GTP or OXT-ATP. Analysis of products synthesized on singly primed M13 single-stranded DNA by DNA polymerase alpha, HSV-II DNA polymerase or HIV RT in the presence of the analogues revealed that OXT-GTP and C-OXT-GTP were incorporated into DNA and caused chain termination mainly at sites one or two nucleotides beyond the cytosine bases on the template.
Homology between two EBV early genes and HSV ribonudeotide reductase and 38K genes (1984)

Computer-matching of amino acid sequences predicted from the complete EBV DNA sequence against the known HSV gene sequences has revealed significant homology between two EBV reading frames and the HSV1 and HSV2 140K and 38K proteins which are associated with ribonucleotide reductase activity. The two genes are arranged tandemly as in HSV though it appears that, unlike HSV, the two mRNAs are not 3' co-terminal. We have mapped two promoters predicted from the DNA sequence for these genes and shown them to be transcribed at a similar stage in the virus life cycle to that of the HSV genes.
Molecular and population genetic analysis of allelicsequence diversity at the human beta-globin locus. (1994)

Allelic sequence polymorphism at the beta-globin locus was investigated in a group of 36 Melanesians. A 3-kilobase fragment containing the gene and its flanking regions was sequenced in 60 normal (beta A) and 12 thalassemic (intron 1, position 5, G-->C) chromosomes. Haplotype relationships between linked polymorphisms were derived by allele-specific PCR amplification and sequencing. Seventeen nucleotide polymorphisms and 2 length variants were identified, and these sites segregated as 17 sequence haplotypes in the normal chromosomes. This haplotype diversity is higher than that expected on the basis of the nucleotide polymorphism observed and is probably due to recombination and gene conversion. Nucleotide diversity at synonymous sites in the sample is 0.14%, suggesting an average age of sequence divergence of approximately 450,000 years, consistent with that expected for a neutrally evolving human nuclear locus.
Novel chondroitin sulfate-binding cationic liposomes loaded with cisplatin efficiently suppress the local growth and liver metastasis of tumor cells in vivo. (2002)

An increased level of chondroitin sulfate (CS) expression on the cell surface is often associated with malignant transformation and the progression of tumor cells. In this study, CSs expressed on highly metastatic tumor cells were used as a target for the selective delivery of anticancer drugs by polyethylene glycol (PEG)-coated liposomes that contained a new cationic lipid 3,5-dipentadecycloxybenzamidine hydrochloride (TRX-20). We found that PEG-coated TRX-20 liposomes (TRX-20 liposomes) bound preferentially to certain CSs, such as CS B, CS D, and CS E, whereas PEG-coated liposomes lacking TRX-20 showed no significant binding to any of the glycosaminoglycans tested. In vitro, TRX-20 liposomes, but not plain PEG liposomes, avidly bound to and were readily internalized by highly metastatic tumor cells such as LM8G5 and ACHN cells, which express large amounts of CS on the cell surface. When TRX-20 liposomes were loaded with cisplatin, they effectively killed the CS-expressing tumor cells in vitro, whereas cisplatin-PEG liposomes lacking TRX-20 were totally ineffective. When injected systemically, TRX-20 liposomes preferentially accumulated in the liver and in solid s.c. LM8G5 tumors. Therapeutic experiments in mice bearing a s.c. LM8G5 tumor revealed that cisplatin-loaded TRX-20 liposomes were significantly more effective in reducing the local tumor growth than cisplatin-loaded plain PEG liposomes or free cisplatin. Furthermore, the cisplatin-loaded TRX-20 liposomes markedly suppressed metastatic spreading of LM8G5 tumor cells to the liver, significantly increasing the survival time of the tumor-bearing mice. These results demonstrate that the CS-targeted delivery of anticancer drugs by novel cationic liposomes represents a potentially useful strategy to prevent the local growth and metastasis, particularly to the liver, of tumor cells that have enhanced expression of CS.
Development and Selection of Edited B Cells in B6.56R Mice (2006)

Tolerance to dsDNA is broken in mice with a high-affinity anti-DNA H chain transgene, 56R, on the C57BL/6 background (B6.56R). B6.56R produce more anti-dsDNA Abs than BALBc.56R. To investigate how anti-DNA Abs are regulated on the B6 background, phenotypic and genetic studies were performed. B6.56R have reduced numbers of B cells and phenotypically altered B cell subsets, including relative increases in the proportions of IgM-negative bone marrow B cells, cells with a marginal zone phenotype, and cells with a transitional T3 phenotype. The peripheral B cell repertoire in B6.56R is restricted: most B cells express the 56R H chain and use a similar, limited subset of editor L chains. DNA binding is more common in B6.56R because the repertoire is shifted toward L chains that are more permissive for DNA binding. H chain editing is also observed and is increased in spontaneous as compared with LPS hybridomas. A subset of spontaneous hybridomas appears to lack H chain expression.
Overexpression of cyclin D1 in mouse skin carcinogenesis. (1993)

Recent studies have provided evidence suggesting that disruption of cyclin function may play a critical role in tumorigenesis. Cyclin D1, a putative G1 cyclin previously isolated in human parathyroid adenomas (designated PRAD1) and mouse macrophages (designated Cyl1), has been implicated in various neoplasias including breast and squamous cell carcinomas (SCC). The role of cyclin altered regulation in the different stages of tumor progression has not been studied in a well defined animal model system. In the study presented here, Cyl1 was mapped to the distal end of mouse chromosome 7 and found to be dramatically overexpressed in skin SCC. In premalignant stages of tumor development, early papillomas showed basal Cyl1 transcript levels, whereas over-expression was observed in most advanced papillomas. These findings suggest that altered expression of cyclin D1 plays a critical role in mouse skin carcinogenesis and may be related to the acquisition of autonomous growth by papillomas. Further studies on the role of cyclin D1 in the mouse model system should prove valuable for understanding the multistep basis of tumor progression.
Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behçet's syndrome (2003)

VEGF may participate in the course of Behçet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.
Drastic Reduction of Plasmon Damping in Gold Nanorods (2002)

The dephasing of particle plasmons is investigated using light-scattering spectroscopy on individual gold nanoparticles. We find a drastic reduction of the plasmon dephasing rate in nanorods as compared to small nanospheres due to a suppression of interband damping. The rods studied here also show very little radiation damping, due to their small volumes. These findings imply large local-field enhancement factors and relatively high light-scattering efficiencies, making metal nanorods extremely interesting for optical applications. Comparison with theory shows that pure dephasing and interface damping give negligible contributions to the total plasmon dephasing rate.