Phase 2 Site Investigations Report. Volume 2 of 3: site-Specific Investigations

1994 ◽  
Author(s):  
ECOLOGY AND ENVIRONMENT INC ARLINGTON VA
Keyword(s):  
Phase 2 ◽  
Site Specific ◽  
Site Investigations

NGSCUP: Phase II trial of site-specific treatment based on gene expression and mutation profiling by next generation sequencing (NGS) for patients (pts) with cancer of unknown primary site (CUP).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15577-e15577
Author(s):  
Hidetoshi Hayashi ◽  
Yuichi Takiguchi ◽  
Hironobu Minami ◽  
Kohei Akiyoshi ◽  
Yoshihiko Segawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Survival Rate ◽  
Specific Treatment ◽  
Diagnostic Technique ◽  
Gene Profiling ◽  
Unknown Primary ◽  
Phase 2 ◽  
Site Specific ◽  
One Year ◽  
Tumor Types

e15577 Background: Although gene profiling is a promising diagnostic technique to determine the tissue of origin for pts with CUP, we reported that site-specific treatment based on gene profiling using microarray did not result in an improvement the survival compared with empirical therapy in the previous randomized phase 2 trial (Hayashi, et. al, JCO 2019). Recently, we have established new integrative diagnostic system combined the gene expression from RNA-sequencing and mutation/copy number variation data from targeted genomic-sequencing using NGS. We have performed a single-arm phase 2 study to assess the efficacy of site-specific therapy determined by this system in previously untreated pts with CUP. Methods: Comprehensive gene profiling was performed by NGS, and an established algorithm was applied to predict tumor origin. Pts with CUP was received site-specific chemotherapy determined by the predicted site. The primary endpoint was one-year survival rate. Results: A total of 111 pts was enrolled and all had sufficient biopsy tissue for gene profiling. Efficacy analysis was performed for 97 pts who received site-specific treatment. Cancer types most commonly predicted were lung (21%), liver (15%), kidney (15%), and colorectal cancer (12%). The one-year survival rate, median overall survival (OS), and progression free survival (PFS) was 53.1% (95%CI, 42.6-62.5%), 13.7 months (95% CI, 9.3-19.7 months), and 5.2 months (95% CI, 3.3-7.1 months), respectively. Median OS (15.7 versus 11.0 months, P = .078) and PFS (5.5 versus 2.8 months, P = .019) were better for predicted tumor types categorized as more responsive types than for less responsive ones. Conclusions: Site-specific treatment based on NGS demonstrated promising efficacy. Pts with CUP predicted to have more responsive tumor types had longer survival compared with pts with less responsive tumor types, suggesting that molecular tumor profiling by both DNA and RNA testing contributes to the management of pts with CUP. Clinical trial information: UMIN051180009.

On the dynamic foundation factor for the National Building Code of Canada: low to medium rise buildings

1994 ◽  
Vol 21 (2) ◽  
pp. 353-356
Author(s):  
A. C. Heidebrecht ◽  
A. Rutenberg
Keyword(s):  
Engineering Design ◽  
Seismic Response ◽  
Earthquake Engineering ◽  
Building Codes ◽  
Building Code ◽  
Building Structures ◽  
Response Factors ◽  
Vibration Period ◽  
Site Specific ◽  
Site Investigations

Site-specific seismic response factors for low-period building structures are presented as an alternative to the recently proposed foundation factor F* for inclusion in the seismic provision of the National Building Code of Canada. These factors are not explicit functions of the site vibration period, and, therefore, are more suitable for the design of small to medium rise buildings for which only limited site investigations are routinely carried out. Key words: earthquake engineering, design spectra, site-specific, building codes.

Large-cluster and combined fluorescent and gold immunoprobes

1996 ◽  
Vol 54 ◽  
pp. 892-893
Author(s):  
Richard D. Powell ◽  
James F. Hainfeld ◽  
Carol M. R. Halsey ◽  
David L. Spector ◽  
Shelley Kaurin ◽  
...  
Keyword(s):  
Metal Cluster ◽  
Sulfonyl Chloride ◽  
Gel Filtration ◽  
Cross Linking ◽  
Site Specific ◽  
Fab Fragments ◽  
Cluster Label ◽  
Covalently Linked ◽  
Texas Red ◽  
Fold Excess

Two new types of covalently linked, site-specific immunoprobes have been prepared using metal cluster labels, and used to stain components of cells. Combined fluorescein and 1.4 nm “Nanogold” labels were prepared by using the fluorescein-conjugated tris (aryl) phosphine ligand and the amino-substituted ligand in the synthesis of the Nanogold cluster. This cluster label was activated by reaction with a 60-fold excess of (sulfo-Succinimidyl-4-N-maleiniido-cyclohexane-l-carboxylate (sulfo-SMCC) at pH 7.5, separated from excess cross-linking reagent by gel filtration, and mixed in ten-fold excess with Goat Fab’ fragments against mouse IgG (obtained by reduction of F(ab’)2 fragments with 50 mM mercaptoethylamine hydrochloride). Labeled Fab’ fragments were isolated by gel filtration HPLC (Superose-12, Pharmacia). A combined Nanogold and Texas Red label was also prepared, using a Nanogold cluster derivatized with both and its protected analog: the cluster was reacted with an eight-fold excess of Texas Red sulfonyl chloride at pH 9.0, separated from excess Texas Red by gel filtration, then deprotected with HC1 in methanol to yield the amino-substituted label.

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

Rationalization and internalization

2001 ◽  
Vol 60 (4) ◽  
pp. 215-230 ◽  
Author(s):  
Jean-Léon Beauvois
Keyword(s):  
Phase 1 ◽  
Facilitatory Effect ◽  
Phase 2 ◽  
Causal Explanations ◽  
Reduction Effect ◽  
Dissonance Reduction

After having been told they were free to accept or refuse, pupils aged 6–7 and 10–11 (tested individually) were led to agree to taste a soup that looked disgusting (phase 1: initial counter-motivational obligation). Before tasting the soup, they had to state what they thought about it. A week later, they were asked whether they wanted to try out some new needles that had supposedly been invented to make vaccinations less painful. Agreement or refusal to try was noted, along with the size of the needle chosen in case of agreement (phase 2: act generalization). The main findings included (1) a strong dissonance reduction effect in phase 1, especially for the younger children (rationalization), (2) a generalization effect in phase 2 (foot-in-the-door effect), and (3) a facilitatory effect on generalization of internal causal explanations about the initial agreement. The results are discussed in relation to the distinction between rationalization and internalization.

MEMORY EFFECTS IN THE FRAGMENTATION OF MOLECULES FOLLOWING SITE-SPECIFIC CORE EXCITATION

1987 ◽  
Vol 48 (C9) ◽  
pp. C9-741-C9-744 ◽  
Author(s):  
W. HABENICHT ◽  
L. A. CHEWTER ◽  
M. SANDER ◽  
K. MÜLLER-DETHLEFS ◽  
E. W. SCHLAG
Keyword(s):  
Memory Effects ◽  
Core Excitation ◽  
Site Specific

Idalopirdin bei Alzheimererkrankung: nicht besser als Plazebo

2018 ◽  
Vol 86 (08) ◽  
pp. 456-457
Keyword(s):  
Phase 2 ◽  
Phase 3 ◽  
Alzheimer Demenz

Die Blockade von Serotoninrezeptoren, insbesondere des Serotonin-Rezeptortyps 5-HT6, als Zusatztherapie in Kombination mit Cholinesterasehemmer, hat in experimentellen Versuchen sowie in einer Phase-2-Studie positive Effekte bei Demenz gezeigt. Im Rahmen eines Phase-3 Entwicklungsprogramms wurde nun die Effektivität des selektiven Serotoninrezeptor-Antagonisten Idalopirdin bei leichter bis mittelschwerer Alzheimer Demenz geprüft.

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