A Low-Voltage Fully Differential Constant-Gm Rail-to-Rail CMOS Operational Amplifier

A low-voltage fully differential CMOS operational amplifier withconstant-g_mand rail-to-rail input and output stages ispresented. It is the fully differential version of a previously realizedsingle-ended operational amplifier where a novel circuit to ensure constanttransconductance has been implemented [1]. The input stage is a rail-to-railstructure formed by two symmetrical OTAs in parallel (the input transistorsare operating in weak inversion). The class-AB output stages have also afull voltage swing. A rail-to-rail input common mode feedback structureallows the output voltage control. Measurements in a 0.7 µ standardCMOS process with threshold voltages of about 0.7 V have been done. Theminimum experimental supply voltage is about 1.1 V. The circuit provides a60 dB low frequency voltage gain and about 1.5 MHz unity gain frequency fora total power consumption of about 0.72 mW at a 1.5 V supply voltage.     

Extended survivability of prostate cancer cells in the absence of trophic factors: increased proliferation, evasion of apoptosis, and the role of apoptosis proteins

This project was undertaken to study the survival properties of various prostate cells, including normal (NHP), BPH (benign prostate hyperplasia), primary carcinoma (PCA), and metastatic prostate cancer cells (LNCaP, PC3, and Du145), in the absence of trophic factors. Cell proliferation and cell death were quantitated by enumerating the number of live cells using MTS/PMS kit and of dead (apoptotic) cells using 4',6-diamidino-2-phenylindole dihydrochloride nuclear staining. These cells demonstrated an overall survivability in the order of BPH < NHP < LNCaP < PC3 < PCA < Du145. Upon growth factor deprivation, NHP/BPH cells rapidly underwent apoptosis, leading to a decreased number of live cells. PCA/PC3/Du145 cells, in contrast, demonstrated an initial phase of aggressive growth during which apoptosis rarely occurred, followed by a "plateau" phase in which cell loss by apoptosis was compensated by cell proliferation, followed by a later phase in which apoptosis exceeded the cell proliferation. LNCaP cells demonstrated survival characteristics between those of NHP/BPH and PCA/PC3/Du145 cells. We concluded that the increased survivability in prostate cancer cells results from enhanced cell proliferation as well as decreased apoptosis. The molecular mechanisms for evasion of apoptosis in prostate cancer cells were subsequently investigated. Quantitative Western blotting was used to examine the protein expression of P53 and P21WAF-1, Bcl-2 and Bcl-X(L) (anti-apoptotic proteins), and Bax, Bak, and Bad (proapoptotic proteins). The results revealed that, upon trophic factor withdrawal, NHP and BPH cells upregulated wild-type p53 and proapoptotic proteins Bax/Bad/Bak and down-regulated the expression of P21. Furthermore, NHP and BPH cells endogenously expressed little or no Bcl-2. In sharp contrast, prostate cancer cells expressed nonfunctional P53 and various amounts of Bcl-2 proteins. Upon deprivation, these cancer cells up-regulated P21 and Bcl-2 and/or BclX(L), lost response to withdrawal-induced up-regulation of Bax/Bad/Bak or decreased or even completely lost Bax expression and expressed some novel proteins such as P25 and P54/55 complex. These data together suggest that prostate cancer cells may use multiple molecular mechanisms to evade apoptosis, which, together with increased proliferation, contribute to extended survivability of prostate cancer cells in the absence trophic factors.     

Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.     

Immune resistance of humans during extended isolation

Analyzed were parameters of the immune reactivity and allergological status of participants in the 135-day chamber experiment with periods of induced psychoemotional strain. Stressful situations gave rise to shifts in the antibody system, i.e. decreased blood levels of ImgA, ImgM, and ImgG, decline in the functional activity of T-lymphocytes, suppression of the cytokinetic activity of lymphocytes-natural killers, and sensibilization to various allergens. Totality of these shifts resembles the ones which are typically seen during initial readaptation to the Earth's conditions on after long-term space mission.     

A hybrid multi-objective optimization algorithm for content based image retrieval

Relevance feedback methods in CBIR (Content Based Image Retrieval) iteratively use relevance information from the user to search the space for other relevant samples. As several regions of interest may be scattered through the space, an effective search algorithm should balance the exploration of the space to find new potential regions of interest and the exploitation of areas around samples which are known relevant. However, many algorithms concentrate the search on areas which are close to the images that the user has marked as relevant, according to a distance function in the (possibly deformed) multidimensional feature space. This maximizes the number of relevant images retrieved at the first iterations, but limits the discovery of new regions of interest and may leave unexplored a large section of the space. In this paper, we propose a novel hybrid approach that uses a scattered search algorithm based on NSGA II (Non-dominated Sorting Genetic Algorithm) only at the first iteration of the relevance feedback process, and then switches to an exploitation algorithm. The combined approach has been tested on three databases and in combination with several other methods. When the hybrid method does not produce better results from the first iteration, it soon catches up and improves both precision and recall.     

Genetic algorithms-based design and optimization of statistical quality-control procedures

In general, one cannot use algebraic or enumerative methods to optimize a quality-control (QC) procedure for detecting the total allowable analytical error with a stated probability with the minimum probability for false rejection. Genetic algorithms (GAs) offer an alternative, as they do not require knowledge of the objective function to be optimized and can search through large parameter spaces quickly. To explore the application of GAs in statistical QC, I developed two interactive computer programs based on the deterministic crowding genetic algorithm. Given an analytical process, the program "Optimize" optimizes a user-defined QC procedure, whereas the program "Design" designs a novel optimized QC procedure. The programs search through the parameter space and find the optimal or near-optimal solution. The possible solutions of the optimization problem are evaluated with computer simulation.     

Caveolin-1 and mitochondrial alterations in regenerating rat liver

The liver has a remarkable ability to regenerate after partial hepatectomy (PH), although the factors governing such ability are still poorly understood. During the prereplicative phase of the regeneration, ultrastructural alterations of periportal hepatocytes were seen, including mitochondrial swelling, abnormal accumulation of lipids, and myelin figures which could lead to the formation of lipid droplets. As it has been hypothesized that caveolin-1 is involved in lipidogenesis and in mitochondrial homeostasis, we aimed to study the subcellular distribution of caveolin-1 in hepatocytes at an early stage following PH. Liver samples were processed for light and electron microscopy at 0 h, 24 h, and 96 h after PH. The expression and subcellular distribution of caveolin-1 was assessed by immunohistochemical and immunocytochemical techniques. Following PH, at 24 h, membranes of altered mitochondria of periportal hepatocytes exhibited significant decrease of caveolin-1 expression compared with control. Myelin figures showing high expression of caveolin-1 were also seen. At 96 h, hepatocytes became ultrastructurally similar to the control liver, and the expression of caveolin-1 on mitochondria showed a moderate increase compared with 24 h after PH. Decrease of expression of caveolin-1 in the altered liver mitochondrial membranes at 24 h following PH, and the high expression of caveolin-1 observed on myelin figures, suggests involvement of caveolin-1 is in both mitochondrial homeostasis and lipidogenesis. Addressing the role played by caveolin-1 during liver regeneration might disclose additional features of mitochondrial homeostasis and lipidogenesis during frequent metabolic liver diseases.     

Calorimetric and thermal analysis investigations of the MF-LaF3 mixtures (m = alkali metal)

A systematic thermodynamic investigation of the LiF-LaF₃, NaF-LaF₃, KF-LaF₃, RbF-LaF₃ and CsF-LaF₃ molten salt systems is reported in the present work. Enthalpy of mixing was measured by direct high temperature calorimetry at temperatures ranging 1046-1183 K. Equilibrium phase diagrams were determined by Differential Scanning Calorimetry (DSC). The same DSC technique was also used to measure the heat capacity, the enthalpies of transition and of fusion for the RbLaF₄ and Cs₃LaF₆ stoichiometric compounds and for some NaF-LaF₃ mixtures. Finally, interactions in the melts were discussed in terms of the Hoch-Arpshofen model.