Mass Sensors Based on Capacitive and Piezoelectric Micromachined Ultrasonic Transducers-CMUT and PMUT.

Microelectromechanical system (MEMS)-based mass sensors are proposed as potential candidates for highly sensitive chemical and gas detection applications owing to their miniaturized structure, low power consumption, and ease of integration with readout circuits. This paper presents a new approach in developing micromachined mass sensors based on capacitive and piezoelectric transducer configurations for use in low concentration level gas detection in a complex environment. These micromachined sensors operate based on a shift in their center resonant frequencies. This shift is caused by a change in the sensor's effective mass when exposed to the target gas molecules, which is then correlated to the gas concentration level. In this work, capacitive and piezoelectric-based micromachined sensors are investigated and their principle of operation, device structures and configurations, critical design parameters and their candidate fabrication techniques are discussed in detail.

Application of correlation coefficients and principal components analysis in stability of quantitative and qualitative traits on rice improvement cultivation.

In order to investigate the stability of qualitative and quantitative traits and choose the most appropriate cultivation method and irrigation regime in rice plants, the experiment was conducted in the form of a split-plot design based on a randomized complete block design in three replications and in two cropping years. The results of compound analysis indicated that the effect of year × irrigation regimes in terms of traits, grain yield, rainfall, productivity 2, number of full grains, number of hollow grains, harvest index, percentage of crushed grains and yield of white rice, the effect of year × Cultivation method characteristics in terms of water consumption, rainfall, productivity 1, number of tillers, plant height, spike length, number of hollow grains, thousand seed weight, small grain percentage and white rice yield and the effect of irrigation regime × cultivation methods in terms of all Traits except traits productivity 2 were significant. The results of the mean comparison of the interaction effect of irrigation regimes and cultivation methods also showed that treatments T1W1, T2W1 and T1W3 are favorable for all evaluated traits. Based on the table of correlation coefficients, correlation diagram and map of the intensity of the correlation in the years of the experiment, it is possible to report the correlation of the grain yield trait with the traits of water consumption, rainfall, plant height, 100- seed weight, full grain number and white rice yield. Also, traits productivity 1, productivity 2 and small grain percentage showed a positive correlation and a negative correlation of these three traits with most of the traits evaluated in the experiment was observed. Based on the analysis of the main components, the first four main components explained the most data variance, and T2W2 and T2W3 treatments were identified as suitable treatments for rice cultivation in terms of the first and second main components.

Evaluation of seedling cultivation and irrigation regimes on yield and yield components in rice plant.

A split-plot experiment was conducted in a randomized complete block design with three replications in two cropping years at Mazandaran Rice Research Institute to study cultivation and irrigation regimes. The main factor is three-level irrigation regimes, permanent irrigation throughout the day (T1), irrigation two days after water disappears from the soil (T2) and permanent soil saturation (T3) the second factor is three-level cultivation methods., Plowless cultivation (W1), stack 60 cm (W2), and stack 80 cm (W3). Based on the results obtained from the combined analysis, the effect of the year was significant in terms of rainfall, productivity 2, number of tillers, number of empty grains, 1000-grain weight, percentage of the crushed grain, and white rice yield. The effect of the main factor was significant for all traits except productivity 1 and plant height. Based on the results of comparing the mean effect of year × treatment, four treatments, without plowing with permanent irrigation throughout the day in the first and second year of the experiment, cultivation without plowing with irrigation two days after water disappears from the soil in the second year of experiment and cultivation without Plowing with permanent saturated irrigation in the first and second years of the experiment was identified in terms of grain yield as suitable planting methods with appropriate irrigation regimes. Based on the results obtained from the polygon view in different years of the experiment, T3W1, T3W2, and T1W1 treatments can be suggested as desirable treatments in terms of irrigation regimes and cultivation methods in this rice cultivar. According to the ranking diagram of treatments based on traits in the years of experimentation, T1W1, T2W2 and T1W3 were introduced as the most desirable treatments for cultivating this rice cultivar.

Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma.

New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM.

Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells.

Hodgkin and Reed Sternberg (H-RS) cells represent the malignant cells in classical Hodgkin's disease. Although derived from germinal center B cells, they do not express surface immunoglobulin. This has been explained by the presence of crippling mutations within the immunoglobulin genes in numerous cases of Hodgkin's disease. As immunoglobulin gene expression in B cells requires an interaction between octamer sites and the transactivating factors Oct-2 and Bob-1, this study addresses the expression of the transcription factors Oct-2 and Bob-1 in H-RS cells. In Hodgkin's disease-derived cell lines, low levels of Oct-2 transcripts but no Oct-2 protein were detected. Transcripts of Bob-1, a B-cell-specific co-factor of Oct-2, could not be observed in these cell lines. Absence of Oct-2 and Bob-1 protein expression in primary H-RS cells was demonstrated by performing immunohistochemistry in 20 cases of classical Hodgkin's disease. H-RS cells stained negative for both proteins in all of the cases analyzed. In conclusion, absence of functional Oct-2 and Bob-1 cells represents a novel mechanism for immunoglobulin gene deregulation in H-RS cells. Lack of Oct-2 and Bob-1 points to a defect in transcription machinery in H-RS cells and is associated with lack of immunoglobulin gene expression in these cells.

Effect of Mg content on the bioactivity and biocompatibility of Mg-substituted fluorapatite nanopowders fabricated via mechanical activation.

The aim of this work was preparation, characterization, bioactivity and biocompatibility evaluation of Mg-substituted fluorapatite (Mg-FA) nanopowders. Mg-FA nanopowders with a chemical composition of Ca10-xMgx(PO4)6F2, with x=0, 0.5, 1, and 2 were prepared by mechanically activated method. The in vitro bioactivity was investigated by soaking the powders in simulated body fluid (SBF) for various time periods to analyze the nucleation and growth of bone-like apatite on the surface of the samples. Cell viability and cell attachment were studied by MTT assay. Results indicated that the bioactivity of all of samples with different Mg content was improved compared with the pure FA. However, the mechanism of bioactivity is different and depends on the amount of Mg substitution. Finally, cell culture suggested that the addition of Mg(2+) has no adverse effect and Mg-FA samples have good biocompatibility. The Mg-FA material shows potential in satisfying the requirements of biomedical applications.

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging.

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.

Changes in the liver parenchyma after proton beam radiotherapy: evaluation with MR imaging.

The objective of this study was to describe magnetic resonance (MR) findings with a 1.5T imager for hepatic parenchymal changes after proton beam radiotherapy. Thirty-two patients who received proton radiotherapy with doses of 50-87 Gy underwent MR imaging 1-75 months (mean 22 months) after the start of irradiation. Axial T(2), T(1)-weighted imaging, and a dynamic study after a gadolinium injection were performed. The irradiated areas showed hypointense in T(1)-weighted images, hyperintense in T(2)-weighted images, and intense and prolonged enhancement on the dynamic study (maximum relative enhancement 441.8%+/-263.3 vs. surrounding liver 145.6%+/-67.7, p<0.0001). T(2) values of the irradiated areas were 50.6 to 65.8 msec greater than in the surrounding liver (p<0.005). The values increased with time, being significantly greater 13 months or longer after the beginning of the therapy than after a period of less than 3 months (p<0.05). Pathologic examinations (n = 3) indicated that the irradiated areas were composed of collapsed lobules with hepatic small vein occlusions, and rich extracellular matrices which retained extracellular fluid. MR imaging can demonstrate hepatic parenchymal changes after proton beam radiotherapy, and show the changes are irreversible.

Central dot sign in entities other than Caroli disease.

OBJECTIVE: The purpose of this study was to describe central dot sign (tiny dots with strong contrast enhancement of the portal vein within dilated hepatic bile ducts on computed tomography) in entities other than Caroli disease, especially in peribiliary cysts with or without autosomal-dominant polycystic kidney disease. MATERIALS AND METHODS: Computed tomography in 74 cases of peribiliary cysts and 134 cases of other liver diseases and states possibly showing central dot sign were retrospectively reviewed to examine the central dot sign. RESULTS: In three cases of peribiliary cysts, some part of the liver showed strongly enhanced portal radicles surrounded completely or partially by low-attenuation, enlarged peribiliary cysts, presenting "central dot sign" on contrast-enhanced computed tomography. CONCLUSION: We suggest that in addition to Caroli disease, some other entities and diseases of the liver may demonstrate central dot sign and this sign should not be considered a specific finding of Caroli disease.

Hepatic peribiliary cysts: increases in size and number on computed tomography.

We report a 71-year-old male patient with multiple hepatic peribiliary cysts. The six-year follow-up through computed tomography (CT) imaging revealed increases in the size (from less than 10 mm to more than 38 mm) and number of the cysts.

Patterns of cytokeratin expression by neoplastic and non-neoplastic epithelium.

Eighty-one epithelial lesions were studied immunohistologically for cytokeratin protein expression using three anticytokeratins CAM 5.2, NCL5D3 and RCK102. Consistent differences were noted between squamous and glandular neoplasms. Squamous and cutaneous carcinomas were found to preferentially express higher molecular weight cytokeratins than adenocarcinomas. In addition, tumours of similar morphology from different sites showed differences in expression of these markers. Differences in pattern were also found between benign and malignant lesions in the case of liver and urinary bladder. Thus the value of cytokeratin profile analysis in characterisation of epithelial neoplasms is confirmed and may be useful in distinguishing benign from malignant tumours in some instances.

Application of genetic algorithm-kernel partial least square as a novel non-linear feature selection method: partitioning of drug molecules.

Genetic algorithm (GA) and partial least squares (PLS) and kernel PLS (KPLS) techniques were used to investigate the correlation between immobilized liposome chromatography partitioning (log Ks) and descriptors for 65 drug compounds. The models were validated using leave-group-out cross validation LGO-CV. The results indicate that GA-KPLS can be used as an alternative modelling tool for quantitative structure-property relationship (QSPR) studies.

Application of artificial neural network to predict the retention time of drug metabolites in two-dimensional liquid chromatography.

Genetic algorithm and partial least square (GA-PLS) and Levenberg-Marquardt artificial neural network (L-M ANN) techniques were used to investigate the correlation between retention time and descriptors for drug metabolites which obtained by two-dimensional liquid chromatography. The applied internal (leave-group-out cross validation (LGO-CV)) and external (test set) validation methods were used for the predictive power of four models. Both methods resulted in accurate prediction whereas more accurate results were obtained by L-M ANN model. The best model obtained from L-M ANN showed a good R(2) value (determination coefficient between observed and predicted values) for all compounds, which was superior to GA-PLS models.

Potential prolongation of PFS in mantle cell lymphoma after R-HyperCVAD: auto-SCT consolidation or rituximab maintenance.

We retrospectively analyzed 44 patients undergoing first-line treatment for mantle cell lymphoma with R-HyperCVAD, with or without rituximab (R) maintenance or auto-SCT. The primary study end point was PFS; secondary end point was overall survival.Median follow up for all patients was 3.3 years. Median age was 54 years, and 95% (n=42) were stage III or IV at diagnosis. In all, 17 patients underwent consolidative auto-SCT and 12 patients received R maintenance. The overall response rate was 95%, with 91% achieving complete response (CR). Median PFS for all patients was 3.5 years. Median PFS was 2.3 years for patients treated with R-HyperCVAD alone vs 3.9 years (P=0.02) with R-HyperCVAD+ R maintenance and 4.5 years (P=0.01) with R-HyperCVAD+ auto-SCT. For patients who did not achieve CR at interim staging, PFS for R-HyperCVAD alone was 1.4 years vs not reached for R-HyperCVAD+ consolidation (either R maintenance or auto-SCT) (P=0.02). PFS for patients with CR at interim staging was 3.3 years vs not reached (P=0.04) after consolidation. Our data suggest potential improvement in PFS when R-HyperCVAD is consolidated with either R maintenance or auto-SCT. This benefit appears particularly significant in those patients who do not achieve CR at interim restaging.

Fulminant hepatic failure: observation with serial CT.

PURPOSE: To determine the imaging characteristics of fulminant hepatic failure at serial computed tomography (CT) and to assess if any CT findings have prognostic value. MATERIALS AND METHODS: In 40 patients, 207 CT scans were analyzed retrospectively. Thirty-four patients had fulminant hepatic failure (acute in seven and subacute in 27), and six had late-onset hepatic failure. Twenty-one patients died of hepatic failure. CT was performed soon after the onset of coma and repeated weekly. Liver volume was measured by tracing the hepatic contour and summing the areas to estimate whole-liver volume. RESULTS: Liver volumes in survivors (n = 19) and nonsurvivors (n = 21), respectively, were 1,090 cm3 +/- 300 and 830 cm3 +/- 240 at initial CT and 1,130 cm3 +/- 310 and 700 cm3 +/- 280 at last CT (P = .0001). III-defined hypoattenuating areas were noted in 20 patients and were distributed in a solitary (n = 13), multiple (n = 6), or diffuse (n = 1) pattern. At follow-up CT, the area of hypoattenuation increased in six patients (five nonsurvivors) and disappeared or markedly decreased in four survivors. An increase in or late occurrence of ascites was noted in 15 patients (14 nonsurvivors, P = .0001). CONCLUSION: Liver volumes at the initial and last CT examinations and an increase in or late occurrence of ascites are useful prognostic findings.

Early radiation effects on the liver demonstrated on superparamegnetic iron oxide-enhanced T1-weighted MRI.

Early radiation-induced liver injury during radiotherapy detected by a particulate reticuloendothelial MR contrast agent (superparamagnetic iron oxide; SPIO) is described in a patient with cholangiocarcinoma. The irradiated hepatic parenchyma appeared as a heterogeneous, less decreased signal intensity area than the nonirradiated area on MR images after SPIO administration. Resultant differences in signal intensity were better visualized on SPIO-enhanced T1-weighted images than SPIO-enhanced T2-weighted images, although SPIO-enhanced T2*-weighted fast field echo imaging was the most sensitive.

Preclinical evaluation of the antiproliferative potential of STI571 in Hodgkin's disease.

STI571 is a selective tyrosine kinase inhibitor with proven therapeutic potential in malignancies expressing c-kit. A strong c-kit and stem cell factor expression was detected in the Hodgkin and Reed Sternberg cell line L1236, but not in 20 primary cases of classical Hodgkin's disease. Proliferation of L1236 cells was neither affected by addition of stem cell factor nor by neutralising anti-stem cell factor antibodies or STI571. Results suggest that patients with Hodgkin's disease may not benefit from therapy with STI571.

Preservation of hypervascularity in hepatocellular carcinoma after effective proton-beam radiotherapy--CT observation.

AIM: The aim of this study was to describe persistence of hypervascularity in proton treated hepatocellular carcinoma at serial follow-up computed tomography (CT). METHODS: Four patients with unresectable solitary hypervascular hepatocellular carcinoma underwent 55-82 Gy proton-beam irradiation for a period of 15-47 days. Follow-up CT including plain, enhanced and dynamic imaging was performed for a period of 9-36 months. RESULTS: Good preservation of arterial blood supply while gradual decrease in tumour size was clearly depicted by dynamic CT. CONCLUSION: We believe that preservation of hypervascularity as judged by enhancement at CT and magnetic resonance imaging, does not necessarily mean that radiotherapy in hypervascular malignant tumours has been unsuccessful.

CT evaluation of hepatic injury following proton beam irradiation: appearance, enhancement, and 3D size reduction pattern.

PURPOSE: The purpose of this study was to investigate the long-term imaging appearances of hepatic injury following proton beam irradiation. The time-attenuation curves, time of appearance and recovery, and 3D size reduction pattern are described in patients of different ages and genders with different irradiation doses, irradiated portals, and Child groups. METHOD: Forty-six patients with hepatocellular carcinoma underwent 50 to 84 Gy proton beam irradiation in periods of 14-52 days. CT including noncontrast and dynamic study was performed every 3 months starting 3 weeks after the end of irradiation. The 3D volume measurement of areas of radiation-induced hepatic injury was performed through incremental dynamic CT images in every follow-up study. CT follow-up study of the patients was done for 12-76 months. RESULTS: Radiation-induced hepatic injury was observed as low attenuation areas on noncontrast CT and enhanced areas on dynamic study in the regions corresponding to the irradiation portals. Of our cases, 67.5% showed the appearance of radiation hepatitis in 3-4 weeks and 95.3% in 3-4 months after the end of irradiation. In both periods, there was a significant delay in the female patients. The time-attenuation curve showed an early and prolonged enhancement of the irradiated regions. The volume reduction pattern of the injured areas was found to be longstanding, exponential, and directed from periphery to the center. CONCLUSION: Early appearance of radiation-induced hepatic injury was found only to be gender dependent, with a tendency to occur with higher irradiated doses; no other parameters affected this phenomenon in our cases. Disappearance of the injured areas, if present, takes a long time (at least 42 months).

STAT3 is constitutively activated in Hodgkin cell lines.

Hodgkin disease (HD) represents a malignant lymphoma in which the putative malignant Hodgkin and Reed-Sternberg cells are rare and surrounded by abundant reactive nonmalignant cells. It has been suggested that cytokines such as interleukin-6 (IL-6) are involved in the pathogenesis of the disease. The expression of the IL-6 receptor (IL-6R) complex and its link to the activation of signal transducers and activators of transcription (STAT) molecules in HD cell lines was investigated. Gel retardation and Western blot analyses revealed a high level of constitutively activated STAT3 in 5 of 7 HD cell lines, which could not be detected in Burkitt lymphoma cell lines. Different levels of IL-6R protein were measured in various HD cell lines: L428 and Dev cells were characterized by very low levels of gp80 and gp130, on KMH2 cells only gp130 but no gp80 was detected, whereas L540, L591, HDLM2, and L1236 were positive for both gp80 and gp130, suggesting a possible autocrine stimulation of STAT3. However, a further increase in STAT3 activation on IL-6 or IL-6/soluble IL-6R stimulation was not observed. Neutralizing monoclonal antibodies against IL-6, gp80, gp130, or both receptor subunits did not affect the proliferation or the constitutive activation of STAT molecules in HD cell lines. However, the tyrosine kinase inhibitor AG490 blocked the constitutive activation of STAT3 and inhibited spontaneous growth of HD tumor cells. The evidence suggests abnormal STAT signaling and growth regulation in Hodgkin cell lines. (Blood. 2001;98:762-770)