High-dose carfilzomib achieves superior anti-tumor activity over lowdose and recaptures response in relapsed/refractory multiple myeloma resistant to low-dose carfilzomib by co-inhibiting the β2 and β1 subunits of the proteasome complex

The optimal carfilzomib dosing is a matter of debate. We analyzed the inhibition profiles of proteolytic proteasome subunits β5, β2 and β1 after low-dose (20/27 mg/m2) versus high-dose (≥36 mg/m2) carfilzomib in 103 pairs of peripheral blood mononuclear cells from patients with relapsed/refractory (RR) multiple myeloma (MM). β5 activity was inhibited (median inhibition >50%) in vivo by 20 mg/m2, whereas β2 and β1 were co-inhibited only by 36 and 56 mg/m2, respectively. Co-inhibition of β2 (P=0.0001) and β1 activity (P=0.0005) differed significantly between high-dose and low-dose carfilzomib. Subsequently, high-dose carfilzomib showed significantly more effective proteasome inhibition than low-dose drug in vivo (P=0.0003). We investigated the clinical data of 114 patients treated with carfilzomib combinations. High-dose carfilzomib demonstrated a higher overall response rate (P=0.03) and longer progression-free survival (PFS) (P=0.007) than low-dose carfilzomib. Therefore, we escalated the carfilzomib dose to ≥ 36 mg/m2 in 16 patients who progressed during low-dose carfilzomib-containing therapies. High-dose carfilzomib recaptured response (≥ partial remission) in 9 (56%) patients with a median PFS of 4.4 months. Altogether, we provide the first in vivo evidence in RRMM patients that the molecular activity of high-dose carfilzomib differs from that of low-dose carfilzomib by co-inhibition of β2 and β1 proteasome subunits and, consequently, high-dose carfilzomib achieves a superior anti-MM effect than low-dose and recaptures response in RRMM being resistant to low-dose carfilzomib. The optimal carfilzomib dose should be ≥ 36 mg/m2 to reach a sufficient anti-tumor activity, while the balance between efficacy and tolerability should be considered in each patient.Bio-organic Synthesi

Mikrooptische Dünnschicht-Komponenten zur Effizienzverbesserung der Kollimation von Diodenlaser-Arrays (MDK)

[no abstract available

High-speed optical-wireless communications for indoor applications

Die drahtlose optische Kommunikation stellt für lokale Anwendungen im Innenbereich eine vielversprechende Ergänzung zu Funksystemen dar. Es wird gezeigt, dass Infrarot-Systeme mit moderner Signalverarbeitung sowohl eine hohe räumliche Abdeckung als auch Bitraten von mehr als 100 Mb/s erreichen, und zwar mit einfachen optischen Komponenten ohne Ausrichtungs- und Nachführungsmechanismen. Farbige LEDs sind für Anzeigen und Signalisierung weit verbreitet, und Weißlicht-LEDs gelten als Hauptkandidat für die allgemeine Beleuchtung der Zukunft. Die Modulation derartiger LEDs erlaubt zugleich Kommunikation mit sichtbarem Licht und somit einen zusätzlichen Dienst zu relativ geringen Mehrkosten. Demonstriert werden Übertragungsraten von mehreren 100 Mb/s bei Beleuchtungsstärken, wie sie Standards für Arbeitsplätze empfehlen

Video broadcast via a lamp

We report the implementation of a real-time visible-light link, based on discrete multitone modulation of a high-brightness LED. Parallel transmission of three high-definition video streams was also demonstrated

A fiber detector radiation hardness test

An intense 146 MeV/c pion beam was stopped inside a scintillating fiber detector made out of 12 planes with 16 pixels each, where every pixel consists out of 8 x 8 scintillating fibers of 500 #mu#m diameter dense packed. The detector was irradiated for 52 hours to more than 1 Mrad at its center. Before and directly after the irradiation the detector has been exposed to a particle beam to compare the corresponding light output. This study was continued during the following three months using cosmic rays. No damage was found taking into account the measurement errors of 5-10%. In contrast a 9 cm deep lucid degrader became irreversibly non-transparent in the irradiation region. (orig.)17 refs.Available from TIB Hannover: RA 2999(99-079) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Hybrid wireless optics (HWO): Building the next-generation home network

Gigabit home access networks (HANs) are a pivotal technology to be developed if the European Union (EU) Vision of the Future Internet is to be realised. Consumers will require such HANs to be simple to install, without any new wires, and easy enough to use so that information services running on the HAN will be "just another utility," as, for instance, electricity, water and gas are today. The hOME Gigabit Access (OMEGA) HAN project [1] aims at bridging the gap between home and access network, providing Gbit/s connectivity to users. The project considers a combination of various technologies such as radio frequency (RF) and free-space or wireless optical links (FSO - operating at infrared and visible wavelengths) in order to meet user demands and provide wireless connectivity within and the home and its surroundings. When combined with power-line communications this enables a home backbone that meets the "without new wires" vision. A technology-independent MAC layer will control this network and provide services as well as connectivity to any number of devices the user wishes to connect to it in any room in a house/apartment, and further, this MAC layer will allow the service to follow the user from device to device. In order to make this vision come true, substantial progress is required in the fields of optical-wireless physical layers, in protocol design, and in system architecture. © 2008 IEEE

Wireless optical network for a home network

During the European collaborative project OMEGA, two optical-wireless prototypes have been developed. The first prototype operates in the near-infrared spectral region and features Giga Ethernet connectivity, a simple transceiver architecture due to the use of on-off keying, a multi-sector transceiver, and an ultra-fast switch for sector-to-sector hand over. This full-duplex system, composed by one base station and one module, transmits data on three meters. The second prototype is a visible-light-communications system based on DMT signal processing and an adapted MAC sublayer. Data rates around to 100 Mb/s at the physical layer are achieved. This broadcast system, composed also by one base station and one module, transmits data up to two meters. In this paper we present the adapted optical wireless media-access-control sublayer protocol for visible-light communications. This protocol accommodates link adaptation from 128 Mb/s to 1024 Mb/s with multi-sector coverage, and half-duplex or full-duplex transmission

Optical wireless communications for broadband access in home area networks

As a part of the EU-FP7 RandD programme, the OMEGA project (hOME Gigabit Access) aims at bridging the gap between mobile broadband terminals and the wired backbone network in homes. To provide Gb/s connectivity a combination of various technologies is considered. Beside radio frequencies, the wireless links will use infrared and visible light. Combined with power-line communications this enables a home area network (HAN) that meets the vision of broadband home networking 'without new wires'. A technology-independent MAC layer is foreseen to control such network and to provide services as well as connectivity to any device the user wishes to connect. Moreover, this MAC layer should allow the service to follow the user from device to device in any room of a building /apartment. The contribution presents ideas and approaches for broadband optical wireless (OW) communications using infrared Gb/s hotspots and 100 Mb/s information broadcasting by means of interior lighting based on white-light LEDs. Important issues concerning the physical layer are discussed. ©2008 IEEE

Mikrooptische Duennschicht-Komponenten zur Effizienzverbesserung der Kollimation von Diodenlaser-Arrays (MDK) Zusammenfassender Schlussbericht

SIGLEAvailable from TIB Hannover: QN1(116,14) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman