gebhart/patrepeval huggingface dataset:
Contributions of Human Tumor Xenografts to Anticancer Drug Development (2006)

Mouse models of cancer have consistently been used to qualify new anticancer drugs for study in human clinical trials. The most used models include transplantable murine tumors grown in syngeneic hosts and xenografts of human tumors grown in immunodeficient mice. For the latter systems, retrospective preclinical-clinical correlation studies are available, which suggest that improvements must be made to increase their value. Transgenic, knock-out, and knock-in mouse models and their intercrosses are more recent developments that mirror defined steps of human carcinogenesis. However, their value in predicting clinical results remains to date poorly defined. We take the position that properly used and interpreted human tumor xenografts grown in immunodeficient mice can be useful, although not absolutely predictive of behavior in the clinic, and continue to make contributions to critical clinical development choices.
Statistical estimations in enzyme kinetics (1961)

Although elementary statistical methods such as the calculation of means and their standard errors are commonly employed, application of the statistical methods of regression analysis in enzyme kinetic studies has received little attention. In estimating the kinetic parameters of the Michaelis-Menten equation, for instance, graphical methods such as the double-reciprocal plot (Lineweaver & Burk, 1934) are generally used, without supple- mentary statistical calculations. These methods have been reviewed by Dixon & Webb (1958).
Inorganic Nanoparticles for MRI Contrast Agents (2009)

Abstract Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of superparamagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionalized with targeting agents have been used for targeted imaging via the site‐specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle‐based T1 contrast agents to overcome the drawbacks of iron oxide nanoparticle‐based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle‐based MRI contrast agents.
Model compounds and monomers for phenylene ether carboranylene ketone (PECK) polymer synthesis: preparation and characterization of boron-arylated ortho-carboranes bearing carboxyphenyl, phenoxyphenyl or benzoylphenyl substituents (2002)

Fourteen new derivatives of ortho-carborane, 1,2-C2B10H12, have been prepared containing functionalized aryl groups attached to one or both of the boron atoms (B9 and B12) antipodal to the carbon atoms, in order to test the suitability of such species for use in the preparation of new categories of phenylene ether carboranylene ketone (PECK) polymers. Model compounds prepared from 9-iodo-ortho-carborane 1 to test synthetic procedures and reactions included the mono-substituted carboranes 9-R1-1,2-C2B10H11 in which the boron attached group R1 was p-tolyl (2), p-HO2CC6H43, p-MeOC6H4COC6H44, p-PhOC6H45 or p-PhCOC6H4OC6H46 (C6H4 represents para-phenylene throughout). Formation of 3 from 2 by CrO3 oxidation showed the capacity of the boron–aryl link to withstand strongly oxidizing conditions. Formation of 4 from 3 and anisole, PhOMe, in trifluoromethane sulfonic acid (TFSA), and of 6 from 5 and benzoic acid, PhCO2H, in TFSA showed such systems could undergo the acylation reactions that would allow polymer formation from suitable diarylcarborane monomers. Compound 7, 9-(3-PhCO-4-PhO-C6H3)-1,2-C2B10H11 an isomer of 6, was also obtained during the synthesis of 6 from 5 and benzoic acid. The diarylcarboranes 9,12-R22-1,2-C2B10H10 with R2 = p-tolyl 9, p-HO2CC6H410 or p-MeOC6H4COC6H411, bearing identical functionalised aryl groups attached to both antipodal boron atoms, were prepared from 9,12-I2-1,2-C2B10H108. Further series of diarylcarboranes 1,9- and 1,12-R32-1,2-C2B10H10, bearing identical aryl groups R3 on one carbon atom (C1) and on the antipodal boron atom (B12), or on the boron atom (B9) antipodal to the unsubstituted carbon atom (C2), have also been prepared and characterized, with R3 = p-tolyl 12, 13, p-HO2CC6H414, 15 or p-MeOC6H4COC6H416, 17.
Diabetic Kidney Disease: A Report From an ADA Consensus Conference (2014)

The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included 1) identification and monitoring, 2) cardiovascular disease and management of dyslipidemia, 3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, 4) glycemia measurement, hypoglycemia, and drug therapies, 5) nutrition and general care in advanced-stage chronic kidney disease, 6) children and adolescents, and 7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD.
Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency following AAV5 Gene Transfer (2012)

The dysferlinopathies comprise a group of untreatable muscle disorders including limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment syndrome, and rigid spine syndrome. As with other forms of muscular dystrophy, adeno-associated virus (AAV) gene transfer is a particularly auspicious treatment strategy, however the size of the DYSF cDNA (6.5 kb) negates packaging into traditional AAV serotypes known to express well in muscle (i.e. rAAV1, 2, 6, 8, 9). Potential advantages of a full cDNA versus a mini-gene include: maintaining structural-functional protein domains, evading protein misfolding, and avoiding novel epitopes that could be immunogenic. AAV5 has demonstrated unique plasticity with regards to packaging capacity and recombination of virions containing homologous regions of cDNA inserts has been implicated in the generation of full-length transcripts. Herein we show for the first time in vivo that homologous recombination following AAV5.DYSF gene transfer leads to the production of full length transcript and protein. Moreover, gene transfer of full-length dysferlin protein in dysferlin deficient mice resulted in expression levels sufficient to correct functional deficits in the diaphragm and importantly in skeletal muscle membrane repair. Intravascular regional gene transfer through the femoral artery produced high levels of transduction and enabled targeting of specific muscle groups affected by the dysferlinopathies setting the stage for potential translation to clinical trials. We provide proof of principle that AAV5 mediated delivery of dysferlin is a highly promising strategy for treatment of dysferlinopathies and has far-reaching implications for the therapeutic delivery of other large genes.
IL-6 up-regulates Mcl-1 in human myeloma cells through JAK / STAT rather than Ras / MAP kinase pathway (1999)

Mcl-1 is an anti-apoptotic member of the Bcl-2 family which is tightly regulated during myeloid and B cell differentiation. We have recently reported that Mcl-1 is expressed in human myeloma cells and that Mcl-1 and Bcl-x(L) expression are correlated. In the current study, we demonstrate that IL-6, a survival factor for the human myeloma cell line MDN, rapidly up-regulates Mcl-1 whereas it has no effect on Bcl-2 protein level. In MDN cells, IL-6 induces both extracellular signal-regulated protein kinase (ERK)1,2 and STAT3 activation whereas STAT1 and STAT5 activation remains undetectable. Furthermore, while investigating the IL-6 signaling pathway leading to Mcl-1 up-regulation, we show that a janus kinase (JAK)-2 inhibitor is able to inhibit both STAT3 activation and Mcl-1 up-regulation whereas an MAP/ERK kinase (MEK) inhibitor has no effect. In conclusion, our data suggest the involvement of the JAK / STAT pathway but not of the Ras / mitogen-activated protein (MAP) kinase pathway in IL-6-induced Mcl-1 up-regulation.
Light Trapping in Silicon Nanowire Solar Cells (2010)

Thin-film structures can reduce the cost of solar power by using inexpensive substrates and a lower quantity and quality of semiconductor material. However, the resulting short optical path length and minority carrier diffusion length necessitates either a high absorption coefficient or excellent light trapping. Semiconducting nanowire arrays have already been shown to have low reflective losses compared to planar semiconductors, but their light-trapping properties have not been measured. Using optical transmission and photocurrent measurements on thin silicon films, we demonstrate that ordered arrays of silicon nanowires increase the path length of incident solar radiation by up to a factor of 73. This extraordinary light-trapping path length enhancement factor is above the randomized scattering (Lambertian) limit (2n(2) approximately 25 without a back reflector) and is superior to other light-trapping methods. By changing the silicon film thickness and nanowire length, we show that there is a competition between improved absorption and increased surface recombination; for nanowire arrays fabricated from 8 mum thick silicon films, the enhanced absorption can dominate over surface recombination, even without any surface passivation. These nanowire devices give efficiencies above 5%, with short-circuit photocurrents higher than planar control samples.
Effects of lactoferrin on collagen gel contractile activity and myosin light chain phosphorylation in human fibroblasts (2001)

When fibroblasts are plated on a type I collagen gel they reduce the size of the gel and the extent of collagen gel contraction reflects the motile activity of the fibroblasts. We found that both bovine and human lactoferrin (Lf) enhanced the collagen gel contractile activity of WI-38 human fibroblasts. Rho inhibitor (exoenzyme C3), Rho kinase inhibitor (Y-27632), myosin light chain kinase inhibitor (ML-7), MEK inhibitor (PD98059) and Src family tyrosine kinase inhibitor inhibited the Lf-enhanced collagen gel contraction. Treatment of fibroblasts with Lf induced the phosphorylation of myosin light chain (MLC) within 30 min. Lf-enhanced MLC phosphorylation was inhibited by Y-27632 and ML-7. These results suggest that Lf promotes the motility of fibroblasts by regulating MLC phosphorylation.
Defining Fibronectin's Cell Adhesion Synergy Site by Site-Directed Mutagenesis (2000)

Fibronectin's RGD-mediated binding to the alpha5beta1 integrin is dramatically enhanced by a synergy site within fibronectin III domain 9 (FN9). Guided by the crystal structure of the cell-binding domain, we selected amino acids in FN9 that project in the same direction as the RGD, presumably toward the integrin, and mutated them to alanine. R1379 in the peptide PHSRN, and the nearby R1374 have been shown previously to be important for alpha5beta1-mediated adhesion (Aota, S., M. Nomizu, and K.M. Yamada. 1994. J. Biol. Chem. 269:24756-24761). Our more extensive set of mutants showed that R1379 is the key residue in the synergistic effect, but other residues contribute substantially. R1374A decreased adhesion slightly by itself, but the double mutant R1374A-R1379A was significantly less adhesive than R1379A alone. Single mutations of R1369A, R1371A, T1385A, and N1386A had negligible effects on cell adhesion, but combining these substitutions either with R1379A or each other gave a more dramatic reduction of cell adhesion. The triple mutant R1374A/P1376A/R1379A had no detectable adhesion activity. We conclude that, in addition to the R of the PHRSN peptide, other residues on the same face of FN9 are required for the full synergistic effect. The integrin-binding synergy site is a much more extensive surface than the small linear peptide sequence.
An image analysis method for assessment of prognostic risk in prostate cancer: a pilot study. (1991)

Fully automated computerized image analysis at medium resolution (1 micron per pixel space) was applied in a study of 17 patients with stage D1 prostate cancer. For this pilot study, patients were selected on the basis of very good or very poor outcome. This selection was made in the hope of identifying morphometric features that are useful in prognostic assessment. Nine patients with good outcome were alive after 7 or more years of follow-up and eight patients with poor prognosis were dead of disease in less than 3 years. All patients were treated with 125I seed implantation to the prostate and pelvic lymph node dissection. Hormone therapy was not administered until the time of distant failure. Routine hematoxylin and eosin tissue sections of lymph nodal tissue bearing metastatic neoplasm were used for this analysis. A minimum of eight scenes per case was analysed. Of 50 measured parameters on each cluster, five (gray level distribution, number of cell clusters per scene, bending energy, average cluster area and cluster polarity) were useful to distinguish patients with good outcome from those with a poor outcome. Thirteen of the 17 patients were correctly classified by image analysis (P = 0.044, Fischer's exact test). By comparison, flow cytometry of the identical tissue samples correctly classified 14 of 17 patients (diploid, good outcome; aneuploid, poor outcome; P = 0.009). Only one patient was incorrectly classified by both image analysis and flow cytometry, implying a complementary prognostic role for the two methods. The encouraging result, successful identification of useful morphometric features, justifies a larger study of unselected patients.
Identification of Lead Compounds as Inhibitors of STAT3: Design, Synthesis and Bioactivity (2015)

STAT3 belongs to the signal transducers and activators of transcription (STAT) family. It has been demonstrated that STAT3 is constitutively activated in many tumors, playing a role in carcinogenesis and tumor progression. For this reason, it has being considered a potential target for cancer therapy. In this context, we have designed, synthesized and evaluated 1,4-dimethyl-carbazole derivatives, targeting the STAT3 protein. Moreover, MTT assay performed on A375 and HeLa, showed significant antiproliferative activity of some of synthesized compounds (3-5). The same compounds (3-5) considerably reduced STAT3 expression, as demonstrated by Western blot analysis. Our multidisciplinary approach shows that 1,4-dimethyl-carbazoles are potential building blocks to develop more affinity ligands of STAT3.
INFECTION OF TOBACCO MESOPHYLL PROTOPLASTS BY TOBACCO MOSAIC VIRUS (1969)

It was proved that the protoplasts prepared from mesophyll of Nicotiana tabacum are infected by tobacco mosaic virus. The infection occurred when purified tobacco mosaic virus particles were added to a protoplast suspension in the presence of poly-L-ornithine. The virus multiplied in these protoplasts to a level of 10(6) virus particles per infected protoplast during 24 hours of incubation. The efficiency of infection was remarkably high, exceeding that by mechanical inoculation of tobacco leaves.
Imaging Neural Stem Cell Fate in Mouse Model of Glioma (2009)

This unit describes a protocol for following the fate of stem cells in real time in a mouse model of glioma. Stem cells and tumor cells can be transduced with lentiviral vectors bearing two different luciferases, firefly luciferase (Fluc) and Renilla (Rluc) luciferase, respectively. With the cells labeled in this manner, bioluminescence imaging can be used to study the fate of stem cells in glioma-bearing brains in vivo.
Methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells. (1998)

Androgen-independent metastatic prostate cancer is characterized by a heterogeneous loss of androgen receptor (AR) expression among tumor cells. In this study, we evaluate DNA hypermethylation as a potential transcriptional regulatory mechanism in AR-negative prostate cancer cell lines. Nucleotide sequence analysis demonstrates an approximately 15-kb CpG island in the AR gene that encompasses the transcription start site and exon 1. Using Southern blotting with methylation-sensitive restriction enzymes and methylation-specific PCR, we find aberrant methylation in the AR expression-negative cell lines Du145, DuPro, TSU-PR1, and PPC1. Incomplete methylation in the AR CpG island is also seen in normal female breast and ovarian tissues consistent with the inactivation of one X chromosome by hypermethylation. In contrast, prostate cancer cell lines LNCaP and PC3 express AR and are unmethylated. Normal prostate epithelial cell strains demonstrate no methylation. Exposure of AR-negative prostate cancer cell lines to 5-aza-2' deoxycytidine, a demethylating agent, induces the reexpression of AR RNA in DuPro and TSU-PR1. This reexpression is associated with a demethylation of this region. Prostate-specific antigen, an androgen-responsive gene, is also specifically induced in these lines after AR reexpression. Therefore, in vitro DNA methylation of the 5' CpG AR island may be associated with the loss of AR expression. Furthermore, our results demonstrate that treatment with demethylating agents may engender the reexpression and function of the androgen receptor in AR-negative cell lines.
Influence of Tongxinluo Capsule on Nailfold Microcirculation in Patients with Unstable Angina Pectoris (2003)

Objetive: To observe the influence on Tongxinluo capsule to probe its Mechanisms. Methods: 66 patients with unstable angina pectoris were randomly divided into common group and Tongxinluo group. Nailfold Microcirculation were observed before and after the treatment. Results: the indices of nailfold microcirculation dectrased after treatment compared with that before treatment ( P 0.05～0.01), Conclusion: Tongxinluo could decrease improve microcirculation and it was effective to treat unstable angina pectoris and in the prevention an treatment of cardio～cerebral vascular diseases.
Routine measurement of IgM, IgG, and IgA rheumatoid factors: high sensitivity, specificity, and predictive value for rheumatoid arthritis. (1997)

Routine measurement of IgM, IgG, and IgA RF by ELISA with rabbit IgG as the antigen and pepsin digestion for the detection of IgG RF provides useful information in the differential diagnosis of patients with arthritis.
Reduction of NOS2 overexpression in rheumatoid arthritis patients treated with anti-tumor necrosis factor ? monoclonal antibody (cA2) (1998)

These results indicate that TNFalpha likely plays an important role in enhancing NOS2 expression in RA, and that the antiinflammatory effects of cA2 treatment may be mediated by a reduction of NO overproduction.
Mismatch negativity in dichotic listening: Evidence for interhemispheric differences and multiple generators (1998)

The characteristics of mismatch negativity (MMN) elicited by dichotic stimulation were examined using frequency-deviant stimuli presented to the right, to the left, or to both sides. The experiment was run twice, once using earphones and once using loudspeakers in free field. With both modes of stimulation, deviants presented in the left, right, or both ears, or tones that were switched between ears, elicited comparable MMNs, with a peak latency of about 180 ms. With earphones, the amplitude of the MMN was bigger at the frontal-lateral right hemisphere sites than at the homologous left-hemisphere sites for all deviance conditions. Scalp current density analysis revealed that deviance in the right side elicited bilaterally equivalent frontal current sinks and a trend towards stronger contralateral current sources at the mastoid sites. In contrast, left side deviance elicited frontal sinks and temporal current sources stronger over the right hemiscalp. These results are compatible with the multiple-generator model of MMN. The attention-related role of the MMN is discussed, suggesting comparable attention mechanisms for vision and audition.
PNA/dsDNA Complexes:  Site Specific Binding and dsDNA Biosensor Applications (2006)

The ability of peptide nucleic acids (PNA) to form specific higher-order (i.e., three- and four-stranded) complexes with DNA makes it an ideal structural probe for designing strand-specific dsDNA biosensors. Higher-order complexes are formed between a dye-labeled charge-neutral PNA probe and complementary dsDNA. Addition of a light-harvesting cationic conjugated polymer (CCP) yields supramolecular structures held together by electrostatic forces that incorporate the CCP and the dye-labeled PNA/DNA complexes. Optimization of optical properties allows for excitation of the CCP and subsequent fluorescence resonance energy transfer (FRET) to the PNA-bound dye. In the case of noncomplementary dsDNA, complexation between the probe and target does not occur, and dye emission is weak. The binding between PNA and noncomplementary and complementary dsDNA was examined by several methods. Gel electrophoresis confirms specificity of binding and the formation of higher-order complexes. Nano-electrospray mass spectrometry gives insight into the stoichiometric composition, including PNA/DNA, PNA(2)/DNA, PNA/DNA(2), and PNA(2)/DNA(2) complexes. Finally, structural characteristics and binding-site specificity were examined using ion mobility mass spectrometry in conjunction with molecular dynamics. These results give possible conformations for each of the higher-order complexes formed and show exclusive binding of PNA to the complementary stretch of DNA for all PNA/DNA complexes. Overall, the capability and specificity of binding indicates that the CCP/PNA assay is a feasible detection method for dsDNA and eliminates the need for thermal denaturing steps typically required for DNA hybridization probe assays.