Sensitivity to chemotherapeutic preparations of anthracycline-resistant strains of murine leukemia P388

P388 leukemia strains resistant to rubomycin and ruboxylnitroxyl derivative of rubomycin were studied for their drug sensitivity. The resistant strains exhibited cross resistance to anthracycline antibiotics, vinca alkaloids, actinomycin D, colchicine. The rubomycin-resistant strain gained significantly higher sensitivity (in comparison with the parent strain and the ruboxyl-resistant strain) to six drugs: cisplatin, sarcolisin, dopan, thiophosphamide, degranol, 6-mercaptopurine. The karyotype of the ruboxyl-resistant cells was characterized by the presence of chromosome with homogeneously straining region (HSR). The alteration of the HSR-location was accompanied by the increase of chemotherapeutical sensitivity of the ruboxylresistant strain to the alkylating agents.     

Phosphorus-containing metabolites in the cells of anthracycline-resistant strains of leukemia P388

The method of 31P nuclear magnetic resonance has been used to study in vivo the level of phosphorus-containing metabolites in cells of two strains of murine leukemia P388 with the phenotype of the multidrug resistance and in cells of the parent strain. Cells of both resistant strains showed a depressed level of phosphomonoesters in comparison with the parent one. The influence of rubomycin and emoksil on the level of phosphorus-containing metabolites of drug-resistant and -sensitive strains has been evaluated. The drugs were established not to affect practically the pool of these metabolites of the resistant strains. Both drugs significantly increased the pool of phosphomonoesters in the parent strain cells.     

Changes in the chemotherapy sensitivity of leukemia L1210 cells during the development of diazan resistance

L 1210 leukemia strain resistant to diazan (L 1210/D1) was studied for its drug sensitivity in comparison with the parent strain. The resistant strain exhibited significantly higher sensitivity to nine drugs: dopan, sarcolysine, apirazidin, cyclophosphane, 6-mercaptopurine, thiophosphamide, rubomycin, vinblastine and vincristine. L 1210/D1 gained cross resistance to four drugs: 1-(2-chloroethyl)-3-(2, 6-dioxy-3-piperidyl)-1-nitrosourea, methotrexate, 5-fluorouracil and ftorafur. The resistant strain sensitivity remained unchanged (in comparison with the parent strain) to seven drugs: degranol, prospidin, nitrosomethylurea, chlorozotocin, deazauridine, bleomycin and L-asparaginase (crasnitine).     

Role of intracellular pH in the development of resistance of leukemic cells to antineoplastic drugs

Intracellular pH (pHi) of mouse lymphoid leukemia P388 cells was measured at the wavelength of 518 and 570 nm of fluorescein: pHi of rubomycin-sensitive P388 cells was higher than pHi of the cells resistant to this antitumour antibiotic (6.98 +/- 0.04 and 6.63 +/- 0.03, respectively, P less than 0.001). The role of pHi is established during induction of the resistance of tumour cells to the antitumour drugs.     

Antineoplastic activity of combinations of cytostatics and dextran-ferrite administered to mice with leukemia P-388

Water solutions of adriblastin, dactinomycin, rosevin, methotrexate, cisplatin, sarcolysine, rubomycin, cyclophosphamide, 5-fluorouracil or ftorafur were combined with dextran ferrite. The obtained compositions were injected i.p. to BDF1 mice 24 hours after they were inoculated with one million of murine P388 leukemic cells. Antitumor activity was fully retained for each of these agents in combination with dextran ferrite.     

Cytogenetic characteristics of the leukemia L1210 strain in the development of drug resistance

The dose and schedule dependent resistance occurred at the 17th (L1210/D1) and 27th (L1210/D2) generations during leukemia L1210 transplantation by the cells treated with suboptimal diazane doses. With growth of the resistance to diazane the selection of modal cell class with 39 chromosomes took place while in the parent leukemia line the modal cell class consists of the cells with 40 chromosomes. No reliable differences were observed in G-banded karyotypes between the resistant subline L1210/D1 and the parent line L1210. When the resistant sublines were transplanted without supporting the diazane doses no restoration of the leukemic cells sensitivity to the drug was observed (the time of observation for L1210/D1 was 92 transplantation generations and for L1210/D2-48 generations). The changed number chromosome characteristics remained the same in this case.     

Endurance Reliability of Multilevel-Cell Flash Memory Using a $ hbox{ZrO}_{2}/hbox{Si}_{3}hbox{N}_{4}$ Dual Charge Storage Layer

The mechanisms of programming/erasing (P/E) and endurance degradation have been investigated for multilevel-cell (MLC) Flash memories using a $hbox{Si}_{3}hbox{N}_{4}$ (NROM) or a $hbox{ZrO}_{2}/hbox{Si}_{3}hbox{N}_{4}$ dual charge storage layer (DCSL). Threshold-voltage $(V_{rm th})$ -level disturbance is found to be the major endurance degradation factor of NROM-type MLCs, whereas separated charge storage and step-up potential wells give rise to a superior $V_{rm th}$ -level controllability for DCSL MLCs. The programmed $V_{rm th}$ levels of DCSL MLCs are controlled by the spatial charge distribution, as well as the charge storage capacity of each storage layer, rather than the charge injection. As a result, DCSL MLCs show negligible $V_{rm th}$-level offsets ($ ≪ $ 0.2 V) that are maintained throughout the $hbox{10}^{5}$ P/E cycles, demonstrating significantly improved endurance reliability compared to NROM-type MLCs.      

The Thermal Resistance of Solder Joints in High Brightness Light Emitting Diode (HB LED) Packages

We present a framework to calculate the thermal resistance of Au–Sn eutectic solder joint $(R_{rm th, Aumathchar"707B Sn,joint})$ in high brightness light emitting diode (HB LED) packages whose heat extraction capability controls the optical efficiency and reliability of HB LEDs. Using the transient thermal measurement combined with the structure function based analytical method and the finite element method, we find that the thermal conductivity $(k)$ of the thin solder joint becomes significantly smaller than the Au–Sn alloy after joining; hence, $R_{rm th, Aumathchar"707B Sn,joint}$ constitutes a large portion of the total $R_{rm th}$ of the package $left(R_{rm th}^{rm PKG}right)$.      

Novel Nano-Scale Conductive Films With Enhanced Electrical Performance and Reliability for High Performance Fine Pitch Interconnect

In this paper, a novel nano-scale conductive film which combines the advantages of both traditional anisotropic conductive adhesives/films (ACAs/ACFs) and nonconductive adhesives/films (NCAs/NCFs) is introduced for next generation high-performance ultra-fine pitch packaging applications. This novel interconnect film possesses the properties of electrical conduction along the $z$ direction with relatively low bonding pressure (ACF-like) and the ultra-fine pitch $({≪ 30}~ mu {rm m})$ capability (NCF-like). The nano-scale conductive film also allows a lower bonding pressure than NCF to achieve a much lower joint resistance (over two orders of magnitude lower than typical ACF joints) and higher current carrying capability. With low temperature sintering of nano-silver fillers, the joint resistance of the nano-scale conductive film was as low as $10 ^{-5}~{rm Ohm}$. The reliability of the nano-scale conductive film after high temperature and humidity test (85$^{circ}{rm C}$/85% RH) was also improved compared to the NCF joints. The insertion loss of nano-scale conductive film joints up to 10 GHz was almost the same as that of the standard ACF or NCF joints, suggesting that the nano-scale conductive film is suitable for reliable high-frequency adhesive joints in microelectronics packaging.      

Hemopoietic precursor cells during the development of carminomycin resistance

A comparative quantitative investigation of colony-forming ability of mouse bone marrow hemopoietic stem cells in the case of ordinary leukemia variant (P-388) and carminomycin-resistant variant (P-388/k) was carried out. Leukemia bearing mice received single injections of increasing doses of carminomycin on the 5th day after transplantation and 24 hours later the bone marrow was investigated for quantity of colony-forming units in the spleen (CFUs). Dynamics investigation of bone marrow cells in the case of P-388 and P-388/k (without treatment) reveals the common tendency to a decrease of these cells in the period before animal death. Sensitivity of colony forming cells (CFUs) to different doses of the antibiotic of mouse bone marrow in both cases (P-388 and P-388/k) was practically the same. Dynamics of CFUs in two populations of cells after a single injection of carminomycin in doses causing the killing of 50% of CFUs showed that the antibiotic inhibited CFUs equally (50%). However this inhibition in case of CFUs with P-388/k leukemia was almost five times longer than in the case of ordinary P-388 one. Based on the investigations conducted the second injection of the antibiotic to mice with P-388/k leukemia on the fifteenth day after the first one may be recommended.     

$V_{rm th}$ Control by Complementary Hot-Carrier Injection for SONOS Multi-Level Cell Flash Memory

In this paper, a complementary hot-carrier injection programming/erasing (P/E) scheme is proposed for accurate threshold voltage $(V_{rm th})$ control for polysilicon–oxide–nitride–oxide–silicon (SONOS) multi-level cell (MLC) Flash memory. Alternate hot electrons (HEs) and hot holes (HHs) are injected by pulse gate and drain biases, and complementary HE and HH injections spontaneously correct the $V_{rm th}$ offsets via a feedback control enabled by the programming and the offset-correcting cycles. The HE and HH fluxes are balanced at a steady state induced by the tunnel oxide potential transformation. Accurate $V_{rm th}$ control is accomplished, and endurance reliability is significantly improved for SONOS MLCs.      

Insight Into the Suppressed Recovery of NBTI-Stressed Ultrathin Oxynitride Gate pMOSFET

It has been observed that the ultrathin oxynitride gate pMOSFET is resistant to post-negative-bias-temperature-instability (post-NBTI) recovery. The resistance to recovery is due mainly to the locking in of stress-induced positive interfacial/bulk oxide defects at deep energy levels (above the conduction band edge of the Si n-well) outside the energy window of electron direct tunneling. As a consequence, these defect states can remain positively charged for a long period in the ultrathin gate dielectric, even under positive gate biasing. Results show that nitrogen increases the density of deep-level oxide defect precursors, thus raising the resistance of the ultrathin gate pMOSFET to post-NBTI recovery.     

Cytological characteristics of carminomycin-resistant P-388 lymphoid leukosis

The carminomycin-resistant strain (P-388/c) of P-388 lymphoid leukemia is obtained. Resistance development is accompanied by higher sensitivity to cytostatics, rise of hyperploidy, replacement of the stem line, presence of definite markers in leukemic cells as well as by the appearance of a clone of cells with higher dry mass. At the level of CFUs after the carminomycin administration more remote terms of cell restoration than in case of P-388/c lymphoid leukemia are determined. The P-388/c lymphoid leukemia cells lost their sensitivity to carminomycin at the stage of the DNA synthesis. Accumulation of cells is observed in phase G2 of the mitotic cycle.     

14Co-dimetinur distribution in mice in relation to the stage of the development of tumor process

Pharmacokinetics of the antitumour agent 14CO-dimetinur (100 mg/kg) after oral administration to the intact mice and those with solid leukemia P 388 is characterized by its rapid delivery to organs and tumours with the achievement of maximum radioactivity 5 hours later and the further gradually decline during 4 days. The increased accumulation of the 14CO-products in kidneys and their retarded output from the brain and lungs against a background of the relatively equal distribution of radioactivity between other tested organs have been established. The same level of carbamoylated products in large tumours (the 16th day after leukemia transplantation) as well as in small tumours (the 9th day after inoculation) is in agreement with the conservation of the initial marked inhibitory effect of the drug against advanced tumours.     

Electrical Instability of RF Sputter Amorphous In-Ga-Zn-O Thin-Film Transistors

Bias-temperature-stress (BTS) induced electrical instability of the RF sputter amorphous In-Ga-Zn-O (a-IGZO) thin-film transistors (TFTs) was investigated. Both positive and negative BTS were applied and found to primarily cause a positive and negative voltage shift in transfer $(I _{rm DS} -V _{rm GS})$ characteristics, respectively. The time evolution of bulk-state density $(N _{rm BS})$ and characteristic temperature of the conduction-band-tail-states $(T _{G})$ are extracted. Since both values showed only minor changes after BTS, the results imply that observed shift in TFT $I _{rm DS} -V _{rm GS}$ curves were primarily due to channel charge injection/trapping rather than defect states creation. We also demonstrated the validity of using stretch-exponential equation to model both positive and negative BTS induced threshold voltage shift $(Delta V _{rm th})$ of the a-IGZO TFTs. Stress voltage and temperature dependence of $Delta V _{rm th}$ evolution are described.      

Enhancement of CW THz Wave Power Under Noncollinear Phase-Matching Conditions in Difference Frequency Generation

We investigated methods for improvement of continuous-wave (CW) terahertz (THz) output power by laser diode (LD) pumping in noncollinear phase-matched difference frequency generation (DFG). The effects of interaction length and beam spot size of input lasers (near-IR) in GaP crystals were studied. The THz wave power dependence on various sizes of GaP crystals was investigated and it was observed that an output power of 4 nW was obtained with a 20 mm long GaP crystal at 1.5 THz. Also, the THz wave absorption coefficient was dominant for longer GaP crystals at high frequencies (above 2.5 THz). The THz wave power dependence on beam spot size (1.2 mm–300 $mu{rm m}$) of near-IR lasers at 1.62 THz was studied, and an improvement of THz wave power being seen with a 500 $mu{rm m}$ beam spot size, while the beam divergence effect was dominant for beam spot sizes below 500 $mu{rm m}$.      

Independent-Double-Gate FinFET SRAM for Leakage Current Reduction

An independent-double-gate (IDG) fin-type MOSFET (FinFET) SRAM has been successfully fabricated with considerable leakage current reduction. The new SRAM consists of IDG-FinFETs which have flexible $V_{rm th}$ controllability. The IDG-FinFET with a TiN metal gate is fabricated by a newly developed gate-separation etching process. By appropriately controlling the $V_{rm th}$ of the IDG-FinFET, we have successfully demonstrated the reduction of the leakage current and power consumption of the SRAM circuitry.      

Response of Grounding Electrodes to Impulsive Currents: An Experimental Evaluation

Experimental results for the transient behavior of grounding electrodes are presented to clarify fundamental aspects of the grounding response to lightning currents. It is shown that for fast current waves, the value of impulsive grounding impedance $Z_{P}$ of short electrodes is smaller than its low-frequency resistance $R_{rm LF}$ while electrodes longer than the effective length have a resistance value smaller than impulsive impedance. The values found for the ratio $Z_{P}/R_{rm LF}$ in the experiments are lower than those resulting from numerical simulation for electrodes shorter than the effective length.      

Strain and Temperature Sensing Characteristics of Single-Mode–Multimode–Single-Mode Structures

We present a comprehensive study of the strain and temperature-sensing characteristics of single-mode–multimode–single-mode (SMS) structures based on the modal interference of guided modes of graded index multimode fiber (MMF) section spliced in between two single-mode fibers. A detailed theoretical study of the structures in terms of the refractive index distribution, effect of dopant and their concentrations, and the variation of core diameter has been carried out. Our study shows that for the SMS structure with a ${rm GeO}_{2}$-doped MMF there exists a critical wavelength on either side of which the spectrum shows opposite spectral shift with a change in temperature/strain, whereas for structures with a ${rm P}_{2}{rm O}_{5}$-doped MMF it shows monotonic red shift with increasing temperature/strain. It has been found that the critical wavelength shifts toward higher wavelengths with decreasing “ $q$” value/doping concentration. Using different MMFs, both the red and blue spectral shifts have been observed experimentally. It has also been found that the SMS structure has higher sensitivity toward this critical wavelength. The study should find application in designing strain-insensitive high-sensitive temperature sensors or vice versa.      

High-Temperature Microwave Performance of Submicron AlGaN/GaN HEMTs on SiC

The effect of temperature on the small-signal radio-frequency (RF) performance of submicron AlGaN/GaN high-electron-mobility transistors on SiC has been studied from room temperature (RT) up to 600 K. A relation between ambient and channel temperatures has been established by means of finite-element simulations. The thermal behavior of the intrinsic parameters $C_{rm gs}$, $C_{rm gd}$, $g_{m, {rm int}}$, and $g_{rm ds}$ has been extracted accurately from RF measurements by means of the small-signal equivalent circuit. Main dc parameters $(I_{D}, g_{m, {rm ext}})$ show reductions close to 50% between RT and 600 K, mainly due to the decrease in the electron mobility and drift velocity. In the same range, $f_{T}$ and $f_{max}$ suffer a 60% decrease due to the reduction in $g_{m, {rm ext}}$ and a slight increase of $C_{rm gs}$ and $C_{rm gd}$. An anomalous thermal evolution of $C_{rm gd}$ at low $I_{D}$ has been identified, which is indicative of the presence of traps.