gebhart/patrepeval huggingface dataset:
50th Anniversary Perspective: There Is a Great Future in Sustainable Polymers (2017)

It is likely that a half-century ago even enthusiastic and optimistic proponents of the synthetic polymer industry (Mr. McGuire included) could not have predicted the massive scale on which synthetic polymers would be manufactured and used today. Ultimately, the future success of this industry will rely on the development of sustainable polymers—materials derived from renewable feedstocks that are safe in both production and use and that can be recycled or disposed of in ways that are environmentally innocuous. Meeting these criteria in an economical manner cannot be achieved without transformative basic research that is the hallmark of this journal. In this Perspective we highlight five research topics—the synthesis of renewable monomers and of degradable polymers, the development of chemical recycling strategies, new classes of reprocessable thermosets, and the design of advanced catalysts—that we believe will play a vital role in the development of sustainable polymers. We also offer our outlook on several outstanding challenges facing the polymer community in the broad area of sustainable polymers.
Absence of interleukin 2 production in a severe combined immunodeficiency disease syndrome with T cells. (1990)

We have characterized a child with a severe combined immunodeficiency disease syndrome with increased numbers, but a normal distribution, of CD3+ T cells. This patient's immunological defect appears to be attributable to a selective deficiency in T cell production of IL-2, which may reflect a subtle abnormality in the IL-2 gene locus or a defect in a regulatory factor necessary for IL-2 transcription. The increased numbers of phenotypically normal T cells in this patient suggest that alternative pathways of T cell development exist in man or that IL-2 production intra- and extrathymically is controlled via distinct regulatory mechanisms.
Cancer Imaging with Radiolabeled Antibodies (2015)

I. Historical and Theoretical Perspectives.- 1. Clinical radioimmunodetection: The second decade.- 2. Antibody targeting: Theoretical considerations.- II. Model Systems.- 3. Experimental model systems for antibody targeting and radioimmunodetection.- 4. Preclinical models and methods for the study of radiolabeled monoclonal antibodies in cancer diagnosis and therapy.- 5. Physiology of monoclonal antibody accretion by tumors.- 6. Intraperitoneal delivery of monoclonal antibodies.- III. Radiochemistry.- 7. Chelates and antibodies: Current methods and new directions.- 8. Radiolabeling antibodies via the cyclic anhydride of DTPA - Experiences of 5 years.- 9. Bifunctional chelating agents for radiometal-labeled monoclonal antibodies.- 10. Optimization of biodistribution by introducing different chemical linkages between antibody and an indium-111 chelate.- 11. Novel bifunctional linkers for antibody chelation with radiometals.- 12. Labeling of anti-tumor antibodies and antibody fragments with Tc-9m.- IV. Clinical Studies.- 13. Requirements for the use of radioimmunodetection of cancer in clinical practice.- 14. In-vivo antibody imaging for the detection of human tumors.- 15. In-111 monoclonal antibody immunoscintigraphy of colorectal cancer.- 16. Tumor targeting with monoclonal antibody B72.3: Experimental and clinical results.- 17. Antibody imaging of endocrine tumors.- 18. Diversity of the human immune response to clinically used murine monoclonal antibodies.- V. New Approaches.- 19. Antibody lymphoscintigraphy.- 20. Radioimmunoguided surgery: A new intraoperative approach to the detection of tumor.- 21. Augmentation of tumor antigen expression by recombinant human interferons: Enhanced targeting of monoclonal antibodies to carcinomas.- 22. Anti-antibody enhancement of tumor imaging.
A Prospective Evaluation of a Simplified Captopril Test for the Detection of Renovascular Hypertension (1990)

• Renovascular hypertension is potentially curable but of low prevalence. A previous retrospective study has demonstrated the use of a potentiated increase in plasma renin activity after captopril administration as a diagnostic test for renovascular hypertension; this requires two blood samples for plasma renin activity determination and three inclusive criteria for a positive test result. We applied this test prospectively to screen 100 hypertensive patients for renovascular hypertension. We evaluated 29 patients with renovascular hypertension; the remainder were diagnosed as having essential hypertension. In our patient population, a postcaptopril plasma renin activity of 5.7 ng of angiotensin per milliliter per hour (ngAI·mL<sup>−</sup>1·h<sup>−1</sup>) or greater had a 100% sensitivity and an 80% specificity for renovascular hypertension. An absolute increase in plasma renin activity with captopril of 4.7 ngAI·mL<sup>−</sup>1·h<sup>−1</sup>or greater had a lower sensitivity of 90% and a specificity of 87%, whereas a fractional increase in plasma renin activity after captopril of 150% or higher had the lowest sensitivity of 69% and a specificity of 86%. A subgroup analysis of 38 patients who were receiving diuretic therapy demonstrated that the test sensitivity was unchanged but the specificity was reduced. In conclusion, a single postcaptopril plasma renin activity value of 5.7 ngAI·mL<sup>−</sup>1·h<sup>−1</sup>or greater is a simplified screening test for renovascular hypertension, with excellent sensitivity and acceptable specificity. This test is well tolerated, inexpensive, and easy to perform. (<i>Arch Intern Med.</i>1990;150:569-572)
Novel Functional Renal PET Imaging With 18F-FDS in Human Subjects (2019)

The novel PET probe 2-deoxy-2-F-fluoro-D-sorbitol (F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in 2 human volunteers. F-FDS was produced by a simple 1-step reduction from F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from F-FDG, F-FDS is virtually available at any PET facility with radiochemistry infrastructure.
Prognostic value of a 46-gene cell cycle progression (CCP) RNA signature for prostate cancer death in a conservatively managed watchful waiting needle biopsy cohort. (2011)

4542 Background: The natural history of newly diagnosed prostate cancer is highly variable and difficult to predict accurately. Improved tools are needed to more appropriately match treatment to a patient’s risk of progression. We previously showed that a 46 gene cell cycle progression (CCP) RNA signature is a robust predictor of biochemical recurrence after radical prostatectomy and of prostate cancer-specific death in a conservatively managed cohort diagnosed by transurethral resection of the prostate. However, the greatest need exists for predicting outcome in patients diagnosed by needle biopsy. Here we report the utility of the CCP score obtained from a needle biopsy in a cohort of conservatively managed watchful waiting patients. Methods: mRNA was extracted from paraffin embedded needle biopsies from UK men diagnosed with clinically localized prostate cancer between 1990 and 1996. RNA levels of 46 genes were determined and a mean composite score calculated (CCP score) for each patient. Clinical variables consisted of centrally re-reviewed Gleason score, baseline PSA, age, clinical stage, and extent of disease (proportion of positive cores). The primary endpoint was death from prostate cancer after a mean follow up of 9.8 yrs. Results: In univariate analysis (n=352), The hazard ratio (HR) for death for prostate cancer was 2.67 (95% CI (1.99,3.58), P =10-10) for a change from the 25th to 75th percentile of the CCP score. In a multivariate analysis (n=333) which included Gleason and PSA, CCP dominated (HR for change from 25th to 75th percentile = 2.07, 95% CI(1.50, 2.85) χ2= 20.8, , P = 5 x 10-6) with only Gleason score providing a significant, additional contribution (χ2= 15, 1df, P = 0.0001) and baseline PSA was nonsignificant (χ2 = 1.6). Conclusions: For patients managed by active surveillance, the CCP score is the strongest predictor of cancer death outcome yet described. The additional independent prognostic information offered by this RNA assay may be valuable in the management of prostate cancer.
Piezoelectric permeabilization of mammalian dermal tissue for in vivo DNA delivery leads to enhanced protein expression and increased immunogenicity (2011)

Electropermeabilization of mammalian cells is a technique that has been used for the delivery of therapeutics, such as DNA plasmids or DNA vaccines. Typically, delivery via electropermeabilization occurs through injection of the substance into the tissue of interest followed by the insertion of electrodes at the site and the application of brief electrical pulses. Here we detail a novel and innovative contactless electropermeabilization method to deliver DNA plasmids to dermal tissue in vivo. This process has the advantage of eliminating the insertion of additional needles that serve as electrodes to facilitate the application of electric pulses in conventional electroporation processes. Plasmid encoding GFP was injected into guinea pig skin and pulsed with the novel contactless electropermeabilization method. Three days following treatment, robust GFP expression was observed on the skin of pulsed animals. Strong humoral immune responses were also achieved when a DNA vaccine expressing the influenza antigen NP was delivered and pulsed using the novel device in comparison to naked injection alone. This delivery method has the advantage of being contactless and suggests that gene transfer via this mode warrants further development.
Abstract A58: Wnt signaling pathway components are associated with telomerase activity in breast cancer (2011)

Abstract Telomerase is a ribonucleoprotein complex that adds TTAGGG repeats to telomeres in a highly regulated fashion. Telomerase activity is absent in normal somatic cells, thus limiting their number of cell divisions due to telomere shortening. In contrast, the large majority of tumor cells upregulate telomerase activity, consistent with their ability to maintain stable telomere lengths and to divide indefinitely. Telomerase activity is detectable in over 90% of breast tumors, and it is well established that telomerase overexpression is an important step in the progression of normal epithelium to invasive breast cancer. In addition to telomerase upregulation, deregulation of various signaling pathways promotes tumor progression and metastasis. To better understand in which cellular pathway telomerase and telomeres are involved, we comprehensively quantified telomerase activity and telomere length in a panel of 52 extensively characterized breast cancer cell lines and correlated these metrics with the expression profiles of the cell lines. Across the entire panel of breast cancer cell lines, expression of 530 genes was significantly correlated with telomerase activity (FDR-corrected p-val &amp;lt; 0.2), while expression of 585 genes was significantly correlated with telomere length. Secondary G0-term analysis revealed that telomere length was significantly associated with genes involved in Alzheimer's disease, apoptosis regulation and negative regulation of transcription. Genes significantly correlated with telomerase activity were associated with apoptosis regulation, DNA repair, nucleotide metabolism and Wnt signaling. Several Wnt target genes, including MYC, KLF5, and FGF18 were also correlated with telomerase activity. We also used the network analysis tool PARADIGM (1) to identify cellular pathways associated with telomerase activity and telomere length. Notably, Wnt signaling components were significantly correlated with telomerase activity. Given the recent evidence that the telomerase component TERT can act as a transcriptional modulator of the Wnt/beta-catenin signaling pathway (2), we are currently testing how Wnt signaling is altered due to telomerase perturbation in breast cancer cells. (1) Vaske, C. J. et al. Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM. Bioinformatics 2010; 26:i237–245 (2) Park, J. I. et al. Telomerase modulates Wnt signaling by association with target gene chromatin. Nature 2009; 460:66–72 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A58.
ChemInform Abstract: Preparation and in vitro Activities of Naphthyl and Indolyl Ether Derivatives of the FK‐506 Related Immunosuppressive Macrolide Ascomycin. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A 33mW 8Gb/s CMOS clock multiplier and CDR for highly integrated I/Os (2004)

A 0.622-8 Gb/s CDR circuit using injection locking for jitter suppression and phase interpolation in high bandwidth SOC solutions is described. A slave injection locked oscillator (SILO) is locked to a tracking aperture-multiplying DLL (TA-MDLL) via a coarse phase selection MUX. For the fine timing vernier, an interpolator DAC controls the injection strength of the MUX output into the SILO. This 1.2 V 0.13 /spl mu/m CMOS CDR consumes 33 mW at 8 Gb/s. Die area, including voltage regulator, is 0.08 mm/sup 2/. Recovered clock jitter is 6.9 ps rms/49.3 ps peak-to-peak at a 200 ppm bitrate offset.
Crossing of disclinations in nematic slabs (1998)

It is shown experimentally that crossing and intercommutation of disclinations in a bounded nematic cell depend on surface orientation of the director and the relative strength of disclinations. Lines of opposite strength switch the pinned ends between the bounding plates and vanish independently of each other if the surface orientation is tangential. In contrast, tilted surface orientation preserves the stability of lines.
Abstract 1266: Downregulation of PD-L1 by NSAID administration augments the effects of a multi-antigen vaccine for the prevention of adenomatous polyps in APC(Min/+) mice (2018)

Abstract Introduction: We have shown that treatment of APC(Min/+) mice with NSAIDs will inhibit development of adenomatous polyps and induce significant levels of polyp-infiltrating CD8 T-cells. We sought to identify the mechanism of NSAID induced immune stimulation and questioned whether administration of NSAIDs concurrent with vaccination could further reduce polyp formation. Methods: PD-L1 expression and T-cell infiltrates were assessed by IHC and flow cytometry. MC38 and RKO (murine/human colorectal carcinoma cell lines) were treated with naproxen (200uM-1000 uM) and harvested at 24, 48 and 72h. At 4-6 weeks, APC(Min/+) mice were given a multi-antigen peptide vaccine (COX2, CDC25B, EGFR) with CFA/IFA or adjuvant alone. Two groups received 400ppm naproxen orally 7d/wk for 18 weeks. Polyps were quantified at ≤24 weeks. Spleens and polyps were collected for IFN-gamma ELISPOT, flow cytometry, and IHC. Results: Polyps from the APC(Min/+) mouse and both cancer cell lines highly express PD-L1. PD-L1 expression was significantly decreased in MC38 (p&amp;lt;0.01) and RKO (p&amp;lt;0.01) as compared to control after incubation with naproxen at all doses. The inhibitory effect of NSAIDs on PD-L1 expression was both time and dose dependent. We evaluated the in vivo effect of combination immunoprevention in the APC(Min/+). Animals receiving vaccine alone showed a 33% inhibition of polyp formation while naproxen alone showed 54% inhibition (p&amp;lt;0.0001) compared to adjuvant alone. Combination treatment demonstrated significantly greater inhibition of polyps than either modality (p&amp;lt;0.001), 81% inhibition vs. adjuvant. Antigen specific T-cells could be detected at higher levels than control antigen in both the vaccine alone (p=0.0001) and combination-treated animals (p&amp;lt;0.0001). The antigen specific responses seen in combination treated animals were nearly two-fold that of vaccine alone (p=0.008). No antigen specific immunity was detected in naproxen and adjuvant only treated mice. The magnitude of the immune response was significantly correlated with lower polyp counts, with a Pearson correlation coefficient of -0.55 (p=0.0014). Detailed immunologic analysis of tumors will be presented. Conclusions: NSAIDs, via modulation of PD-L1, synergize with vaccines to increase immunogenicity and enhance influx of polyp infiltrating lymphocytes. This synergy results in superior prevention of polyp formation compared to treatment with NSAID or vaccine alone and has high potential for clinical application. Citation Format: Mary L. Disis, Lauren R. Corulli, Clinton Grubbs, Ronald A. Lubet, Paul Cowan, Ekram Gad. Downregulation of PD-L1 by NSAID administration augments the effects of a multi-antigen vaccine for the prevention of adenomatous polyps in APC(Min/+) mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1266.
Discovery of a Potent, Selective, and Orally Bioavailable Pyridinyl-Pyrimidine Phthalazine Aurora Kinase Inhibitor (2010)

The discovery of aurora kinases as essential regulators of cell division has led to intense interest in identifying small molecule aurora kinase inhibitors for the potential treatment of cancer. A high-throughput screening effort identified pyridinyl-pyrimidine 6a as a moderately potent dual inhibitor of aurora kinases -A and -B. Optimization of this hit resulted in an anthranilamide lead (6j) that possessed improved enzyme and cellular activity and exhibited a high level of kinase selectivity. However, this anthranilamide and subsequent analogues suffered from a lack of oral bioavailability. Converting the internally hydrogen-bonded six-membered pseudo-ring of the anthranilamide to a phthalazine (8a-b) led to a dramatic improvement in oral bioavailability (38-61%F) while maintaining the potency and selectivity characteristics of the anthranilamide series. In a COLO 205 tumor pharmacodynamic assay measuring phosphorylation of the aurora-B substrate histone H3 at serine 10 (p-histone H3), oral administration of 8b at 50 mg/kg demonstrated significant reduction in tumor p-histone H3 for at least 6 h.
Reconstruction of the proximal humerus for bone neoplasm using an anatomic prosthesis-bone graft composite. (2012)

This study assesses function after limb sparing bone tumour resections of the proximal humerus. Twenty-seven patients had an intraarticular resection with reconstruction using an anatomic prosthesis-bone graft composite with average clinical follow-up of 63 years (range: 13-15.8 years). Pain relief was achieved for 22 shoulders (81%); 19 of 25 patients responding (76%) were satisfied. Active elevation averaged 62 degrees, external rotation 25 degrees, and internal rotation to L-4. Complications included instability in 7, nonunion in 4, implant loosening in 3 of these and tumour recurrence in 1. There were 7 reoperations. Using the Neer rating, 19 primary operations (70%) were successful. The Musculoskeletal Tumor Society Score averaged 18.5 (62%), the American Shoulder and Elbow Surgeons functional score 18.4 (37%) with a total score of 51 (51%), and on the Simple Shoulder Test 5.4 of 12 questions were answered affirmatively. This procedure is oncologically safe. There are structural complications, notably shoulder instability. Function ratings are one-third to one-half normal.
Supplementary Table from ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody (2023)

Supplementary Table from ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody
Iterative reconstruction using a pyramid-shaped basis function (2012)

In iterative reconstruction, it is common to represent the continuous image as a finite linear combination of basis functions. Popular basis functions include the B-splines and the blobs. It turns out that the B-spline of order 0 corresponds to nearest-neighbour interpolation, and its parallel-beam projections are piecewise linear functions. Also, the B-spline of order 1 corresponds to bilinear interpolation and its parallel-beam projections are piecewise cubic polynomials. This observation brings the question of whether there exists an intermediate basis function with parallel-beam projections taking the form of a piecewise quadractic polynomial. Here, we discuss image reconstruction using a pyramid-shaped basis function that satisfies this condition. It turns out that this function performs as well as the B-splines of order 1 in terms of bias and noise. Unfortunately, reconstruction with this basis function requires a correction method to remove an inconvenient grid pattern.
Figure S6 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (2023)

&lt;p&gt;Supplementary Figure 6: Gene Set Enrichment Analysis reveals immune-related pathways discriminate PD and SD tumors.&lt;/p&gt;
Shear-ordered face-centred cubic photonic crystals (2000)

Large-area face-centred cubic photonic crystals are fabricated by the two-dimensional shear-alignment of stabilised 720 nm diameter PMMA spheres dispersed in an epoxy resin. The resulting crystal is made permanent by exposure to UV light, thus solidifying the epoxy resin. The technique is rapid and produces high quality, large-area crystals.
Varying results for immunoassay screening kits for cotinine level. (2002)

Our earlier study found that although enzyme-linked immunosorbent analysis (ELISA) screening assays for urine cotinine indicated use in former smoking treatment patients who reported abstinence, this finding was sometimes incorrect when validated against gas chromatography/mass spectrometry (GC/ MS; P. Gariti, A. I. Alterman, R. Ehrmann, F. D. Mulvaney, & C. P. O'Brien, 2002). In the current validation study, separate urine samples of 71 of these same patients were reanalyzed by an independent laboratory in blinded fashion using a screening enzyme immunoassay (EIA) analysis and GC/MS confirmation. EIA results showed almost total agreement with confirmatory testing. The findings indicate that use of screening ELISA/EIA for urine cotinine can detect unreported cases of smoking in former patients, but that care is needed in selecting a laboratory for conducting these tests.
Acyclic analogs of 3'-azido-3'-deoxythymidine as potential antiviral agents. Nucleoside synthesis by Michael addition (1989)

An acyclic derivative of 3'-azido-3'-deoxythymidine, (R,S)-1-[1-(2-hydroxyethoxy)-3-azidopropyl]thymine (2), has been synthesized by a path involving Michael-type addition. Related thymidine analogues lacking the C(3')-C(4') bond were similarly obtained. The method provides a versatile new route to nucleoside analogues. The new compounds were found to be essentially inactive against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro when tested up to 100 microM.