924 research outputs found
Synthetic DNA immunotherapy in biochemically relapsed prostate cancer
Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).
Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) \u3e3 months (mos), testosterone \u3e150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks.
Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = \u3c0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = \u3c0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50).
Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213)
Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis
BACKGROUND: Increased serum levels of procalcitonin (ProCT) and its component peptides have been reported in humans with sepsis. Using a hamster model of bacterial peritonitis, we investigated whether serum ProCT levels are elevated and correlate with mortality and hypocalcemia. RESULTS: Incremental increases in doses of bacteria resulted in proportional increases in 72h mortality rates (0, 20, 70, and 100%) as well as increases in serum total immunoreactive calcitonin (iCT) levels at 12 h (250, 380, 1960, and 4020 pg/ml, respectively, vs control levels of 21 pg/ml). Gel filtration studies revealed that ProCT was the predominant (> 90%) molecular form of serum iCT secreted. In the metabolic experiments, total iCT peaked at 12 h concurrent with the maximal decrease in serum calcium. CONCLUSIONS: In this animal model, hyper-procalcitoninemia was an early systemic marker of sepsis which correlated closely with mortality and had an inverse correlation with serum calcium levels
An exploratory study of how a Korean chaebol’s learning culture facilitates customer service
This paper explains how the organizational learning concept is used by managers in a global Korean company to promote group work, information sharing and an open communication style in order to produce a high level of customer service. Previously collected data from a set of in-depth personal interviews undertaken with three senior managers in a Korean electronics company were analyzed and interpreted using the grounded theory approach, and a number of propositions are put forward. The research findings show that managers in a chaebol deploy organizational learning to identify skilled and knowledgeable staff, and improve the organization’s capability by placing emphasis on developing harmonious, mutually oriented relationships that permeate throughout the organization. Top management demand that staff identify with government economic objectives and align the organization’s strategy accordingly so that the products produced are marketable. To achieve this, the organization fosters continual interaction among managers throughout the organization’s hierarchy. The chaebol’s organizational learning model encapsulates a “corollary” (continual communication) and “tools” (cultural influence and relationship management), and manifests in a unique strategy that allows management systems to evolve naturally
Massive Charged Scalar Quasinormal Modes of Reissner-N\"ordstrom Black Hole Surrounded by Quintessence
We evaluate the complex frequencies of the normal modes for the massive
charged scalar field perturbations around a Reissner-N\"ordstrom black hole
surrounded by a static and spherically symmetric quintessence using third order
WKB approximation approach. Due to the presence of quintessence, quasinormal
frequencies damp more slowly. We studied the variation of quasinormal
frequencies with charge of the black bole, mass and charge of perturbating
scalar field and the quintessential state parameter.Comment: 9 pages, 9 figures and one tabl
Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green alga Chromochloris zofingiensis
Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (-Fe). Cells grown in -Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production
Outward expansion of the lunar wake: ARTEMIS observations
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95030/1/grl29516.pd
Router-level community structure of the Internet Autonomous Systems
The Internet is composed of routing devices connected between them and
organized into independent administrative entities: the Autonomous Systems. The
existence of different types of Autonomous Systems (like large connectivity
providers, Internet Service Providers or universities) together with
geographical and economical constraints, turns the Internet into a complex
modular and hierarchical network. This organization is reflected in many
properties of the Internet topology, like its high degree of clustering and its
robustness.
In this work, we study the modular structure of the Internet router-level
graph in order to assess to what extent the Autonomous Systems satisfy some of
the known notions of community structure. We show that the modular structure of
the Internet is much richer than what can be captured by the current community
detection methods, which are severely affected by resolution limits and by the
heterogeneity of the Autonomous Systems. Here we overcome this issue by using a
multiresolution detection algorithm combined with a small sample of nodes. We
also discuss recent work on community structure in the light of our results
- …