Purpose
Most of the cancer chemotherapy treatments employ drugs in combination. For combination treatments, it is relevant to assess interaction between two or more anticancer agents used in clinics. ...Based on clinical data and using modeling techniques, the work analyzes the pharmacodynamic interaction between capecitabine and docetaxel used in combination in metastatic breast cancer.
Methods
We developed mathematical models to describe tumor growth inhibition profile under treatment based on Phase II and Phase III clinical data of capecitabine and docetaxel in metastatic breast cancer. Model parameters were estimated by population approach with NONMEM
®
on single-agent and combination data. Simulations were performed using MATLAB.
Results
Capecitabine and docetaxel combination in metastatic breast cancer results in a synergistic effect as compared with the simple additive effects of single-agent treatments. Docetaxel is more efficient than capecitabine at the start of treatment but develops resistance faster. Modeling revealed no resistance of capecitabine for the combination data.
Conclusions
Modeling could be a powerful tool to design the most advantageous combination regimen for capecitabine and docetaxel in metastatic breast cancer in order to increase the time before regrowth and decrease the tumor size at regrowth.
Tungsten oxide (WO
3) films with thicknesses ranging from 30 to 100
nm were grown by Hot Filament Vapor Deposition (HFVD). Films were studied by X-Ray Photoemission Spectroscopy (XPS) and were found ...to be stoichiometric. The surface morphology of the films was characterized by Atomic Force Microscopy (AFM). Samples had a granular form with grains in the order of 100
nm. The surface roughness was found to increase with film thickness. HFVD WO
3 films were used as conducting interfacial layers in advanced hybrid organic–inorganic optoelectronic devices. Hybrid-Organic Light Emitting Diodes (Hy-OLEDs) and Organic Photovoltaics (Hy-OPVs) were fabricated with these films as anode and/or as cathode interfacial conducting layers. The Hy-OLEDs showed significantly higher current density and a lower turn-on voltage when a thin WO
3 layer was inserted at the anode/polymer interface, while when inserted at the cathode/polymer interface the device performance was found to deteriorate. The improvement was attributed to a more efficient hole injection and transport from the Fermi level of the anode to the Highest Occupied Molecular Orbital (HOMO) of a yellow emitting copolymer (YEP). On the other hand, the insertion of a thin WO
3 layer at the cathode/polymer interface of Hy-OPV devices based on a polythiophene–fullerene bulk-heterojunction blend photoactive layer resulted in an increase of the produced photogenerated current, more likely due to improved electron extraction at the Al cathode.
Optically controlled self-assembled quantum dots have received substantial attention in the quantum computing area, as techniques for initializing, manipulating, and reading out single spin qubits ...have been demonstrated in essence. The electron-spin coherence and hole-spin coherence are limited due to noisy quantum effects, and there is a significant need for further evaluation and investigation studies. In this work, the behavior of charge noise and spin noise for a fundamental logic unit of four qubit embedded in an AlAs/GaAs heterostructure is reported based on the modeling and simulation approach in the atomic level to provide a more in-depth analysis and evaluation of quantum noise. The numerical calculations are based on reliable simulation methods, which are consistent with experimental results. The approach presented here can become the basis for scaled-up advanced simulations expanding to larger logical blocks of qubits.
Latch-up effects in two stage cascaded CMOS digital inverters due to high power pulsed electromagnetic interference, are reported. Latch-up was observed to occur at and above 25.5
dB
m of pulsed ...interference at frequencies of 1.23
GHz and 4
GHz. When a latch-up event occurred, the devices failed to respond to the input logic signal even after the pulsed interference was removed. Devices required to be reset to return to normal operation. Latch-up for pulsed interference at the higher frequency of 4
GHz occurred at higher power levels, indicating a suppression of the interference effects at higher frequencies due to the by-pass path effects provided by the intrinsic device capacitances. High power interference induced excess carriers and the corresponding body currents that activated the parasitic bipolar transistor action were found to play a key role in triggering the latch-ups, and are proposed here as the main mechanism for the upsets. The parasitic resistances R1 and R2 for the cascaded inverters were calculated to be 4.3 and 2.8
kΩ, respectively, and the corresponding excess body currents triggering the latch-ups were 0.163 and 0.25
mA, respectively.
The primary goal of phase I studies in oncology is to determine the MTD (Maximum Tolerated Dose) for a drug. This MTD is determined with respect to an accepted risk (usually 33%) to see a limiting ...toxity for patients. In this paper we propose a new mathematical model to determine the MTD. An important feature of this model is that the limiting toxicity can be formulated as a combination of several basic graded toxicities such as hematologic or neurological. Another feature is the possibility to take into account several patient covariates to individualize the determination of the MTD. The model is a bayesian model where some prior information has been considered. The model is expected to work better than traditional empirical schemes for determining the MTD because it uses at every step all the available information on patients, and adds some major improvements as compared with existing CRM strategies because it uses whole data made available, including low-grades toxicities. Finally the model has been validated with a retrospective data set on 17 patients from a phase I study on paclitaxel in pediatric oncology. Calculated MTDs for each patient were found to be markedly different than the doses actually given following a traditional dose-escalation methodology. Results suggest that our new model provides a better and safer way to drive dose-escalation in phase-I trials as compared with traditional schemes.
Summary
This research reports the development of an RF sensor integrated circuit (IC) chip capable of tracking the directionality of RF remote emissions. The IC design uses an angle‐of‐arrival ...algorithm, and it is designed for the 180 nm CMOS technology and applicable to other technologies, also. The sensor chip requires two pairs of antennas aligned and placed at distance s for detection of azimuthal and polar angles of the RF incident wave. The circuit consists of custom designed low‐noise amplifiers (LNAs) at the front end, with a novel design of double‐balanced Gilbert cell mixers (GCMs). This amplifies and mixes the signals from the antennas and converts the phase difference Δφ into an equivalent output voltage map suitable for an 18‐bit analog to digital converter. Systematic optimization techniques were developed to maximize the third‐order intercept point and suppress flicker noise for the LNAs and GCMs, resulting in improved sensing accuracy. The overall system‐level evaluation results showed state‐of‐art angle‐of‐arrival sensing capability with an upper limit error of 3.447°.
This research reports the development of an RF sensor IC chip capable of tracking the directionality of RF remote emissions. The sensor chip amplifies and mixes the signals from the antennas and converts the phase difference Δφ
into an equivalent output voltage map. Systematic optimization techniques were developed to maximize the third‐order intercept point and suppress flicker noise for the LNAs and GCMs, resulting in state‐of‐art angle‐of‐arrival sensing accuracy with an upper limit error of 3.447°.
The effects of electromagnetic interference (EMI) from high-power microwave signals on the operational integrity of CMOS inverters are reported. The static characteristics of inverters were measured ...with and without the injection of microwave signals at power levels of upto 24 dBm and frequencies between 800 MHz and 3 GHz. Voltage transfer characteristics showed significant changes in output voltages, and substantial reduction in gain with microwave interference, due to increased drain currents and reduced transconductance, respectively. The asymmetry of the MOS devices (size, mobility) designed to provide balanced current driving capability, results in significantly imbalanced current driving capabilities under interference. A substantial increase in the static power dissipation at the stand-by "ON" and/or "OFF" states, is observed. Degradation in the noise margins and severely compressed input/output voltage ranges were observed due to large changes in voltage characteristics, invalidating noise immunity of cascaded CMOS inverters, and leading to serious bit-flip errors. The load-line characteristics showed substantial shift in the quiescent point of operation, and changes in the effective "ON" resistance of the MOS devices, resulting in increased current in the inverters. The input/output voltage range-related bit-flip errors and the static power dissipation problems, represent the most critical vulnerabilities in the operational integrity of digital systems.
Display omitted
► Undoped and Ni-doped ZnO thin films on (100) silicon substrates were developed by PLD. ► P-type conductivity was found to be dominant at room temperature. ► Cr Schottky contacts ...were deposited on p-type ZnO films. ► I–V characteristics of the Cr/ZnO Schottky diodes were measured at room temperature. ► Barrier heights were determined by using the Cheung–Cheung and Norde models.
Wide band gap semiconducting layers of undoped and Ni-doped p-type ZnO thin films were developed on (100) silicon substrates by pulsed laser deposition (PLD) at a constant oxygen partial pressure of 1.0×10−4 Torr and at constant temperature of 250°C. The electrical properties of the films were studied by resistivity and Hall coefficient measurements at room temperature. P-type conductivity was found to be dominant in these films at room temperature although the incorporation of Ni dopants caused a reduction in the p-character of ZnO films. The surface morphology of the films was evaluated by contact mode atomic force microscopy (AFM) in air. Cr-Schottky contacts were deposited on these p-type ZnO films, and the rectifying properties of the contacts were evaluated. The current–voltage (I–V) characteristics of the Cr/ZnO Schottky diodes were measured at room temperature. Due to series resistance, the Cheung and Cheung functions were used to determine the barrier height and ideality factor of the diodes while Norde function was used to determine barrier height. Ideality factors of 1.07 and 1.22 were obtained for the Cr/undoped ZnO and Cr/Ni-doped ZnO diodes, respectively, while the barrier height was 0.59eV by the Norde model, and in good agreement with 0.62eV of the Cheung–Cheung model, for both undoped and Ni-doped samples.
PDF
