823 research outputs found
The Myth of Ephraim Tutt
No full textThe Myth of Ephraim Tutt explores the true and previously untold story behind one of the most elaborate literary hoaxes in American history. Arthur Train was a Harvard-educated and well-respected attorney. He was also a best-selling author. Train’s greatest literary creation was the character Ephraim Tutt, a public-spirited attorney and champion of justice.Guided by compassion and a strong moral compass, Ephraim Tutt commanded a loyal following among general readers and lawyers alike—in fact, Tutt’s fictitious cases were so well-known that attorneys, judges, and law faculty cited them in courtrooms and legal texts. People read Tutt’s legal adventures for more than twenty years, all the while believing their beloved protagonist was merely a character and that Train’s stories were works of fiction. But in 1943 a most unusual event occurred: Ephraim Tutt published his own autobiography. The possibility of Tutt’s existence as an actual human being became a source of confusion, spurring heated debates. One outraged reader sued for fraud, and the legendary lawyer John W. Davis rallied to Train’s defense. While the public questioned whether the autobiography was a hoax or genuine, many book reviewers and editors presented the book as a work of nonfiction. In The Myth of Ephraim Tutt Molly Guptill Manning explores the controversy and the impact of the Ephraim Tutt autobiography on American culture. She also considers Tutt’s ruse in light of other noted incidents of literary hoaxes, such as those ensuing from the publication of works by Clifford Irving, James Frey, and David Rorvik, among others. As with other outstanding fictitious characters in the literary canon, Ephraim Tutt took on a life of his own. Out of affection for his favorite creation, Arthur Train spent the final years of his life crafting an autobiography that would ensure Tutt’s lasting influence—and he was spectacularly successful in this endeavor. Tutt, as the many letters written to him attest, gave comfort to his readers as they faced the challenging years of the Great Depression and World War II and renewed their faith in humanity and justice. Although Tutt’s autobiography bewildered some of his readers, the great majority were glad to have read the “life” story of this cherished character.https://digitalcommons.nyls.edu/fac_books/1102/thumbnail.jp
South Pacific Tropical Upper Tropospheric Trough (TUTT): variability and impact on the French Polynesian climate
No full textThe South Pacific Tropical Upper Tropospheric Trough (TUTT) is an elongated trough that appears in summer monthly averaged maps of the upper tropospheric flow over the ocean. We provide the first comprehensive description of the South Pacific TUTT and analyze its impact on the regional climate with 42 yr (1979-2020) of monthly data from ERA5, radiosonde, rain, keraunic data, and lightning flash rate from the Optical Transient Detector-Lightning Imaging Sensor. The data confirm the presence of the TUTT along a southeast-northwest axis from November to May. Located between 100 and 400 hPa, the TUTT is a cold-core with a relative vorticity minimum and a negative geopotential anomaly. Divergent, ascending flow with high relative humidity is found south and west of the TUTT axis, while convergent, descending flow with low relative humidity is observed north and east of the TUTT axis. The seasonal and long-term impacts of the TUTT on the local and regional climate is dependent on its location and its strength. The existence of the TUTT in the South Pacific is strongly dependent on the El Niño-Southern Oscillation (ENSO) phases, being stronger during a strong negative ENSO phase and disappearing from French Polynesia during a strong positive ENSO phase. Genesis of tropical disturbances east of 180°W is possible only if the TUTT is located east of 120°W. The environmental conditions associated with the TUTT, along with lightning and rainfall data from 3 sites in French Polynesia, show that lightning flash rates are higher during a negative ENSO phase than during a positive ENSO phase.</jats:p
The influence of Tutt cells on tropical cyclone motion in the northwest Pacific Ocean
No full textA conceptual model of how a TUTT cell can influence TC track is presented. The model provides quantified, decision-grade operational guidance for TC forecasters using pattern recognition scenarios. Application of the conceptual model at the JTWC is currently underway.Eleven tropical cyclones (TCs) are examined using the latest ECMWF reanalysis (ERA-40) and JTWC best track data to determine how tropical upper tropospheric trough (TUTT) cells influence TC tracks. This type of interaction has led to enormous TC track forecast errors at 72 hour (2000+ km) in the northwest Pacific and are often overlooked and under-forecast frequently due to poor numerical model TUTT cell forecasts. Cases are selected because a TC exhibited a "non-standard" track, a TUTT cell was the sole large-scale transient feature within 2000 km of the TC's center, and the TC intensity was >17 m s -1. Analysis shows that the circulations' separation distance, orientation, intensity, and the depth and breadth of the TUTT cell's closed circulation are critical characteristics in determining the likelihood of a TUTT cell influencing a TC's track. Interactions occur at distances greater than 1700 km, continue for periods ranging from 24 to 48 hours and happen 2-3 times per year in this active TC basin.Examination of the TC's deep layer mean (DLM), upper, middle and lower layers along with various quadrants of the upper layer (100-500 hPa) demonstrate a link between the TUTT cell's wind field and the non-standard TC tracks. The TC's 5°-7° mass-weighted DLM steering environment is found to be closest to actual TC motion in most cases. TC intensity variations and circulation proximity sometimes results in the DLM's 3°-5° radial band being closer to actual TC motion.Ph.D
Development, validation and application of ELISAs for pharmacokinetic and HACA assessment of a chimeric anti-CD40 monoclonal antibody in human serum
No full textAs part of a Phase I chimeric anti-CD40 monoclonal antibody clinical trial, two enzyme-linked immunosorbent assays (ELISAs) were developed for secondary endpoints: 1) for the pharmacokinetic (PK) monitoring of serum antibody levels and 2) for immunogenic screening of human anti-chimeric antibody (HACA) responses. The ELISA is a well established immunoassay, with clear guidelines for validation when used as a quantitative assay. However, these parameters may not always be relevant for a semi-quantitative assay used to assess whether a sample is positive or negative for a novel marker such as an antibody developed against a therapeutic antibody. We report here the development of a quantitative PK ELISA and a semi-quantitative HACA ELISA, and the different approaches of validation to prove each assay are ‘fit for purpose.’ The parameters of linearity (R2 > 0.99), accuracy (±30%), lowest level of detection (4 ?g/ml), intra-assay (coefficient of variation (CV) < 20%) and inter-assay (CV < 20%) variability were assessed for the quantitative PK assay. For the semi-quantitative HACA assay, parameters of linearity (R2 > 0.99), lowest level of detection, intra (CV < 10%) and inter-assay (CV < 30%) variability were assessed using a surrogate positive control. The validation outcome showed that each assay was robust, reliable and accurate to meet the requirements of the intended analytical application, that being to 1) quantitatively determine the concentration of antibody in the serum and 2) determine whether a sample is positive or negative for human anti-chimeric antibodies. Each assay has been successfully translated for use in a clinical trial with adequate quality controls and acceptance criteria set for monitoring consistency and performance.<br/
Targeting TAO kinases using a new inhibitor compound delays mitosis and induces mitotic cell death in centrosome amplified breast cells
No full textThousand-and-one amino acid kinases (TAOKs) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11-15 nM, is ATP-competitive and targets these kinases selectively. TAOK inhibition or depletion in centrosome amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death and inhibits cell growth. In contrast, non-tumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome amplified cancer cells preferentially, whilst sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur
Dissertatio Theologica, Super Actor. 26, 10. 11. De Reformatione Ecclesiae
No full textQuam ... Sub Praesidio ... Georg. Henrici Kelleri ... Disputandam proponit Author M. Joh. Christophorus Cucuel, Tutt. SS. Th. Stud. in Duc. Stip. Ad dies & Ian
Juvenile Justice System
No full textARTICLES: : 1. Editorial 2. Youth justice - crisis or opportunity? - N. Tutt 3. American juvenile justice: method and madness - M. Klein 4. The juvenile court: an endangered species? - J. Doek 5. Beyond rehabilitation: in search of a constructive alternative in the judicial response to juvenile crime - L. Walgrave 6. Will the juvenile justice system survive? - J. Junger-Tas 7. Varia: A. Marek on organized crime in Poland: how to combat it? 8. H.-J. Albrecht on sentencing and disparity - a comparative study; 9. International bibliography of J. Junger-Tas 10. Crime institute profile: School of Forensic Science and Criminolog
Voucher funds in transitional economies : the Czech and Slovak experience
No full textVoucher funds have arisen in the transitional economies of Eastern and Central Europe that have used voucher privatization. These funds collect vouchers from citizens and use them to buy shares in enterprises. In the Czech and Slovak Republics, voucher funds are typically organized as corporations owned by the citizens who contributed their vouchers. Recently, they have also been organized as unit trusts (either open-ended or closed). A management company manages the funds under a contract that specifies the management fee. The management company is typically owned by the initial sponsor of the fund - for example, a bank. Voucher funds can give owners a diversified and professionally managed portfolio. More important, the funds select who sits on an enterprise's governance boards (which oversee management and profitability). Although experience is limited, the funds in these two countries have probably stopped most fraud and self-serving by enterprise mangers and are beginning to encourage the restructuring needed for profitability. A few funds have replaced poorly performing or dishonest managers; more often, because qualified replacements are few, they encourage managers to improve performance. There have been complaints about funds'performance. Some have made unrealistic promises to voucher holders and have appointed poorly qualified members to management boards. There is concern about conflicts of interest in the bank-sponsored funds and excessive control of enterprises. Funds typically lack capital or expertise to undertake restructuring - but few other potential owners are likely to be better qualified. The author examines 27 regulations that have been proposed for funds. Regulations in transitional economies, unlike regulations in most western countries, should encourage funds to play a strong role in corporate governance, he contends, as few potential owners have this ability. Most important, regulations should require that funds disclose information about their operations so their owners can monitor and control fund managers. The regulatory regime, the author says, should discourage monopolies and anticompetitive behavior; create incentives for fund managers to improve fund performance; discourage self-serving or fraudulent behavior by fund managers, and conflicts of interest; and eliminate high-risk investments unacceptable to fund owners. Because there is so little experience with these funds, the regulatory regime should not be unduly restrictive. As problems arise, regulations to deal with them can be added.International Terrorism&Counterterrorism,Economic Adjustment and Lending,Economic Theory&Research,Agricultural Knowledge&Information Systems,Payment Systems&Infrastructure
Incidental prostate carcinoma: 4-year follow-up folowing treatment with cyproterone acetate,IL CARCINOMA PROSTATICO INCIDENTALE: QUATTRO ANNI DI FOLLOW-UP DOPO TERAPIA CON CIPROTERONE ACETATO
No full texttutt
The untapped potential of radiation and immunotherapy for hormone receptor-positive breast cancer.
No full textHormone receptor-positive breast cancers are a diverse group of tumours, with only some responding well to immunotherapy. Alternative combination strategies such as radiotherapy present an exciting opportunity to improve immunotherapy responses. We review an intriguing overlap between the impact of oestrogen signalling and radiation on multiple signalling pathways and immune cells that may be exploited for therapeutic gains in breast cancer. This is synthesised with the pre-clinical data and clinical trial landscape supporting the use of combined radiation and immunotherapy to derive insights for future neo-adjuvant trial design
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