162,274 research outputs found
[Report to Chief J. E. Curry, by an unknown author #1]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
[Report to Chief J. E. Curry, by an unknown author #2]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
Murder on the mountain: author talk with Peter J. Wosh
No full textAuthor talk by Peter J. Wosh on May 5th, 2022, on his book, "Murder on the Mountain: crime, passion, and punishment in gilded age New Jersey.
Targeting ALK and WIP1 : neuroblastoma precision medicine under development
No full textNeuroblastoma is the childhood solid tumor accountable for the largest number of deaths, calling for improved treatment. Some genetic alterations are considered crucial in driving initiation and progression of neuroblastoma. These are usually associated with poor prognosis and are viewed as potential therapeutic targets. Anaplastic lymphoma kinase (ALK) is one of the best-established disease drivers in neuroblastoma, harboring oncogenic mutations or amplifications in about 10-15 % of all cases. In 2013, results from the first phase I study of an ALK inhibitor in neuroblastoma, crizotinib, were announced showing disappointing clinical response. Improved later-generation ALK inhibitors have since become available while biological and clinical understanding of ALK mutations in neuroblastoma has increased.In Paper I, a patient with a metastatic high-risk neuroblastoma suffered extreme toxicity due to an underlying condition, Fanconi anemia, prohibiting further conventional treatment. Whole genome sequencing of tumor material revealed a novel ALK variant, ALK-I1171T, which was identified as a potent gain-of-function mutant resistant to crizotinib, but sensitive to later-generation ALK inhibitors including ceritinib. It was shown that ceritinib was equally effective as crizotinib in a panel of ALK-driven neuroblastoma cell lines. As a result, the child could be offered ceritinib in monotherapy, achieving complete metastatic remission and enabling resection of the primary tumor, and long-term survival.In Paper II, activation of ALK as well as tropomyosin-related kinase A (TRKA) was observed in the absence of corresponding genomic alterations in an infant with metastasized and treatment-refractory neuroblastoma. A novel germline mutation of the ALK ligand ALKAL-2 was revealed by whole genome sequencing, which in cell culture and drosophila experiments was shown to be functional. Since an inhibitor targeting both ALK and TRKA was available in entrectinib, this drug was tested in neuroblastoma cell lines. Subsequently entrectinib treatment could be offered to the patient, producing a prompt improvement of clinical status and a gradual decline of catecholamine markers and metastases over the course of several years.The majority of high-risk neuroblastomas contain a gain of chromosome 17q, a feature that correlates with aggressive disease and poor prognosis. The gene PPM1D is situated within the gained region and encodes the phosphatase WIP1, an inhibitor of p53 and a negative regulator of DNA damage response. WIP1 is often overexpressed in neuroblastoma, and overexpression in transgenic mice predisposes to tumor formation. In Paper III we showed that WIP1 expression correlates to 17q gain in neuroblastoma and medulloblastoma cell lines, which are also highly dependent on WIP1. Knockdown of WIP1 delayed tumor growth. Among different small molecule WIP1 inhibitors evaluated, SL-176 was demonstrated to be effective in all tested cell lines regardless of p53 mutational status. Pharmacologic inhibition of WIP1 with SL-176 in xenograft-bearing mice curbed tumor growth.To achieve an improved cytotoxic effect, a drug combination screening with the WIP1 inhibitor SL-176 was conducted in Paper IV, identifying combination with epigenetic modification by inhibition of the histone demethylase JMJD3 as the most synergistic strategy. Combination of SL-176 and the JMJD3 inhibitor GSK-J4 showed strong synergism in a panel of neuroblastoma cell lines with regard to cell viability, WIP1 downstream targets, cell cycle arrest and apoptosis. Pathway analysis of differentially expressed genes, as identified by RNA sequencing, revealed enrichment of genes involved in pathways associated with DNA damage response.While ALK inhibitors are already available to a subset of neuroblastoma patients, WIP1 is a promising therapeutic target where much work remains before patients may potentially benefit. It is our conviction that in the future, targeted therapy will be available to all high-risk neuro-blastoma patients. This thesis represents a few small steps on the road to accomplish that goal.List of scientific papersI. Guan J*, Fransson S*, Siaw JT*, Treis D*, Van den Eynden J, Chand D, Umapathy G, Ruuth K, Svenberg P, Wessman S, Shamikh A, Jacobsson H, Gordon L, Stenman J, Svensson PJ, Hansson M, Larsson E, Martinsson T, Palmer RH, Kogner P, Hallberg B. Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib. Cold Spring Harbor Molecular Case Studies. 2018 Aug 1;4(4):a002550. *These authors contributed equally to the manuscript and share primary authorship. https://doi.org/10.1101/mcs.a002550 II. Treis D*, Umapathy G*, Fransson S*, Guan J, Mendoza-García P, Siaw JT, Wessman S, Gordon Murkes L, Stenman J, Djos A, Elfman LHM, Johnsen JI, Hallberg B, Palmer RH, Martinsson T, Kogner P. Sustained Response to Entrectinib in an Infant With a Germline ALKAL2 Variant and Refractory Metastatic Neuroblastoma With Chromosomal 2p Gain and Anaplastic Lymphoma Kinase and Tropomyosin Receptor Kinase Activation. JCO Precision Oncology. 2022 Jan;(6):e2100271. *These authors contributed equally to the manuscript and share primary authorship. https://doi.org/10.1200/PO.21.00271 III. Milosevic J, Treis D, Fransson S, Gallo-Oller G, Sveinbjörnsson B, Eissler N, Tanino K, Sakaguchi K, Martinsson T, Wickström M, Kogner P, Johnsen JI. PPM1D Is a Therapeutic Target in Childhood Neural Tumors. Cancers (Basel). 2021 Nov 30;13(23):6042. https://doi.org/10.3390/cancers13236042 IV. Treis D, Tümmler C, Åkerlund E, Pepich A, Seashore-Ludlow B, Sakaguchi K, Kogner P, Johnsen JI, Wickström M Targeted inhibition of PPM1D and histone H3K27 demethylase activity synergistically suppress neuroblastoma growth. [Manuscript]</p
Mr. Melvin J. Collier, RWWL AUC, June 2011
No full textThis video is a conversation with Mr. Melvin J. Collier. Mr. Collier talks about his book, "From Mississippi to Africa: A Journey of Discovery". Daniel Le, AUC Woodruff Library, is the interviewer
A Tripartite Post-Recession Rebalancing
No full textIn this latest Advance & Rutgers Report, entitled “A Tripartite Post-Recession Rebalancing,” Dean James W. Hughes and Professor Joseph J. Seneca deliver an incisive assessment of the current market conditions and obstacles in the path of our economic recovery. They offer a statistical cautionary tale that the private and public sector need to hear and acknowledge in order for the economy to make continued progress.This report was published as Issue Paper Number 7, November 2011, in Advance & Rutgers Report
Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′
No full textFirst evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)
The vanishing author in computer-generated works: a critical analysis of recent Australian case law
No full textAbstract
The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
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