Evolution of collaboration and optimization of impact: self-organization in multinational research

Scientometrics - The expanding presence of multinational research teams highlights the importance of characterizing the outcomes of international collaboration. Herein, we characterize the...     

A low-phase-noise K-band CMOS VCO

A novel circuit topology for low-phase-noise voltage controlled oscillators (VCOs) is presented in this letter. By employing a PMOS cross-coupled pair with a capacitive feedback, superior circuit performance can be achieved especially at higher frequencies. Based on the proposed architecture, a prototype VCO implemented in a 0.18-/spl mu/m CMOS process is demonstrated for K-band applications. From the measurement results, the VCO exhibits a 510-MHz frequency tuning range at 20GHz. The output power and the phase noise at 1-MHz offset are -3dBm and -111dBc/Hz, respectively. The fabricated circuit consumes a dc power of 32mW from a 1.8-V supply voltage.     

Artificial neural networks and statistical modeling for electronic stress prediction using thermal profiling

Electronic components are constantly under stress due to factors such as signal density, temperature, humidity, and high current and voltage. Relatively little research has emphasized stress-level prediction under voltage stress. The purpose of this paper was to develop an electronic thermal profile model for stress-level prediction utilizing neural network (NN) and statistical approaches, such as multivariate regression models. Electronic components were removed from boards, subjected to different levels of stress, then replaced. An infrared camera was then used to capture information about component temperature changes over time under normal operating and stress conditions. Statistical analysis of the captured images suggests a strong correlation between thermal profiles and voltage stress levels. Artificial neural network (ANN) and statistical approaches were used to model temperature change profiles for components that had been stressed at different levels, and their predictive ability was compared. Separate data sets were used for model development and model verification. ANN prediction rates were around 70%, compared to 30% for the statistical approach. Experiments were also conducted to evaluate the robustness of the ANN model to the presence of noise in the data. Results suggested that the ANN model was able to accommodate the presence of noise. Various backpropagation (BP) learning algorithms were also evaluated and yielded similar average error rates. A 3-2-1 ANN topology performed better than 3-3-1 or 3-2-2-1 topologies, perhaps because the 3-2-1 topology has a higher data sample to nodes ratio than the other topologies.     

Inhibition of intratracheal lung cancer development by systemic delivery of E1A

Amplification or overexpression of HER-2/neu in human lung cancer has been correlated with poor prognosis and chemoresistance. We have previously reported that the adenovirus type 5 early region 1A (E1A) gene product can suppress HER-2/neu-mediated transformation phenotypes through inhibition of HER-2/neu expression. To find an efficient way to treat HER-2/neu-overexpressing lung cancer with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce E1A into HER-2/neu-overexpressing and low expressing human lung cancer cell lines. Tumour cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction in HER-2/neu-overexpressing lung cancer cell lines. In HER-2/neu low expressing cell lines, E1A could not inhibit cell growth in vitro but could reduce the colony formation ability in soft agarose, indicating different effects of E1A in these two types of cancer cells. To test the therapeutic efficacy of E1A to lung cancer by systemic delivery in vivo, tumor-bearing mice were established by intratracheal injection of lung cancer cells and treated by i.v. tail injections of Ad.E1A(+). As a result, Ad.E1A(+) suppressed HER-2/neu overexpression and inhibited intratracheal lung cancer growth. However, no significant tumor suppression effect of Ad.E1A(+) was observed in mice bearing HER-2/neu low expressing cell line when the same therapeutic procedure was followed. Thus, we conclude that systemic delivery of Ad.E1A(+) can efficiently achieve therapeutic effect in HER-2/neu-overexpressing lung cancer in vivo.     

Baclofen: intestinal absorption mechanism in mice

Systemic lupus erythematosus (SLE) is a multisystem organ disease, and involvement of the gastrointestinal system is relatively rare. We describe a 13-year-old girl who presented initially with abdominal pain, diarrhea, edema, and hypoalbuminemia. She was diagnosed with protein losing enteropathy (PLE) based on the significant increase of alpha 1-antitrypsin clearance in the stool. Two weeks after admission she developed clinical and serological findings that fulfilled the ACR criteria for SLE. Over 22 cases of lupus associated PLE have now been reported, but only 3 in children. Children with PLE should be evaluated for SLE. In addition, PLE should be suspected as a possible cause of unexplained edema and/or hypoalbuminemia in SLE.     

Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes

Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV.