Wave techniques for noise modeling and measurement

The noise wave approach is applied to analysis, modeling, and measurement applications. Methods are presented for the calculation of component and network noise wave correlation matrices. Embedding calculations, relations to two-port figures-of-merit, and transformations to traditional representations are discussed. Simple expressions are derived for MESFET and HEMT noise wave parameters based on a linear equivalent circuit. A noise wave measurement technique is presented and experimentally compared with the conventional method

A 10-Watt X-Band Grid Oscillator

A 100-transistor MESFET grid oscillator has been fabricated that generates an effective radiated power of 660 W at 9.8 GHz and has a directivity of 18.0 dB. This corresponds to a total radiated power of 10.3 W, or 103 mW per device. This is the largest recorded output power for a grid oscillator. The grid drain-source bias voltage is 7.4 V and the total drain current for the grid is 6.0 A, resulting in an overall dc-to-rf efficiency of 23%. The pattern of the SSB noise-to-carrier ratio was measured and found to be essentially independent of the radiation angle. The average SSB noise level was -87 dBc/Hz at an offset of 150 kHz from the carrier. An average improvement in the SSB noise-to-carrier ratio of 5 dB was measured for a 100-transistor grid compared to a 16-transistor gri

ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

The effect of ZD1839 (‘Iressa’), a specific inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor, on the radiation response of human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in vivo. ZD1839 (0.5 μM, incubated days 1–5) significantly increased the anti-proliferative effect of fractionated radiation treatment (2 Gy day−1, days 1–3) on LoVo cells grown in vitro (P=0.002). ZD1839 combined with either single or fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a highly significant increase in tumour growth inhibition (P⩽0.001) when compared to treatment with either modality alone. The radio-potentiating effect of ZD1839 was more apparent when radiation was administered in a fractionated protocol. This phenomenon may be attributed to an anti proliferative effect of ZD1839 on tumour cell re-population between radiotherapy fractions. These data suggest radiotherapy with adjuvant ZD1839 could enhance treatment response. Clinical investigation of ZD1839 in combination with radiotherapy is therefore warranted

Wave computations for microwave education

The analysis of even simple microwave circuits can involve complicated calculations. It is argued that students repeatedly forced through this exercise are left exhausted and never develop understanding and insight into the principles of high-frequency circuit design. The use of computer-aided design software eliminates the network analysis burden, but it is a precarious solution: students easily become dependent on software and never develop analytical skills. A simple wave computational approach to microwave network analysis is discussed. The method is derived from Mason's theory of signal flow graphs and is based on wave variables and scattering parameters. The approach is easily understood and applied as either an analytical tool, or within a microwave CAD analysis engine. PC software using this computational technique is described and its educational applications are discussed

Noise waves and passive linear multiports

Noise waves are a powerful means for characterizing noise in microwave circuits. A simple derivation is given for the relation between a passive circuit's noise-wave correlation matrix and its scattering matrix. It is shown that this relation, referred to as Bosma's theorem, can be readily derived from the fundamental principle that a passive multiport in thermodynamic equilibrium with reflectionless terminations produces uncorrelated output waves

Deciphering signatures of mutational processes operative in human cancer.

The genome of a cancer cell carries somatic mutations that are the cumulative consequences of the DNA damage and repair processes operative during the cellular lineage between the fertilized egg and the cancer cell. Remarkably, these mutational processes are poorly characterized. Global sequencing initiatives are yielding catalogs of somatic mutations from thousands of cancers, thus providing the unique opportunity to decipher the signatures of mutational processes operative in human cancer. However, until now there have been no theoretical models describing the signatures of mutational processes operative in cancer genomes and no systematic computational approaches are available to decipher these mutational signatures. Here, by modeling mutational processes as a blind source separation problem, we introduce a computational framework that effectively addresses these questions. Our approach provides a basis for characterizing mutational signatures from cancer-derived somatic mutational catalogs, paving the way to insights into the pathogenetic mechanism underlying all cancers

Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics

Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the high prevalence of these driver mutations, it may be possible to utilise these alterations as diagnostic adjuncts in clinical practice. Here, we explored the spectrum of H3.3 mutations in a wide range and large number of bone tumours (n 5 412) to determine if these alterations could be used to distinguish GCT from other osteoclast-rich tumours such as aneurysmal bone cyst, nonossifying fibroma, giant cell granuloma, and osteoclast-rich malignant bone tumours and others. In addition, we explored the driver landscape of GCT through whole genome, exome and targeted sequencing (14 gene panel). We found that H3.3 mutations, namely mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB. Overall our observations suggest that the presence of H3F3A p.Gly34 mutations does not entirely exclude malignancy in osteoclast-rich tumours. However, H3F3A p.Gly34 mutations appear to be an almost essential feature of GCT that will aid pathological evaluation of bone tumours, especially when confronted with small needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of GCT should be made with caution

Bioassay-guided isolation and identification of antimicrobial compounds from thyme essential oil by means of overpressured layer chromatography, bioautography and GC-MS

A simple method is described for efficient isolation of compounds having an antibacterial effect. Two thyme (Thymus vulgaris) essential oils, obtained from the market, were chosen as prospective materials likely to feature several bioactive components when examined by thin layer chromatography coupled with direct bioautography as a screening method. The newly developed infusion overpressured layer chromatographic separation method coupled with direct bioautography assured that only the active components were isolated by means of overrun overpressured layer chromatography with online detection and fractionation. Each of the 5 collected fractions represented one of the five antimicrobial essential oil components designated at the screening. The purity and the activity of the fractions were confirmed with chromatography coupled various detection methods (UV, vanillin-sulphuric acid reagent, direct bioautography). The antibacterial components were identified with GC-MS as thymol, carvacrol, linalool, diethylphthalate, and alpha-terpineol. The oil component diethyl-phthalate is an artificial compound, used as plasticizer or detergent bases in the industry. Our results support that exploiting its flexibility and the possible hyphenations, overpressured layer chromatography is especially attractive for isolation of antimicrobial components from various matrixes

Array-based evolution of DNA aptamers allows modelling of an explicit sequence-fitness landscape

Mapping the landscape of possible macromolecular polymer sequences to their fitness in performing biological functions is a challenge across the biosciences. A paradigm is the case of aptamers, nucleic acids that can be selected to bind particular target molecules. We have characterized the sequence-fitness landscape for aptamers binding allophycocyanin (APC) protein via a novel Closed Loop Aptameric Directed Evolution (CLADE) approach. In contrast to the conventional SELEX methodology, selection and mutation of aptamer sequences was carried out in silico, with explicit fitness assays for 44 131 aptamers of known sequence using DNA microarrays in vitro. We capture the landscape using a predictive machine learning model linking sequence features and function and validate this model using 5500 entirely separate test sequences, which give a very high observed versus predicted correlation of 0.87. This approach reveals a complex sequence-fitness mapping, and hypotheses for the physical basis of aptameric binding; it also enables rapid design of novel aptamers with desired binding properties. We demonstrate an extension to the approach by incorporating prior knowledge into CLADE, resulting in some of the tightest binding sequences

An Alternative Approach for Designing Microwave Circuits using a Personal Computer

A computer-aided design (CAD) program, Puff, for designing microwave integrated circuits is presented. The program runs on an IBM PC, PS/2, or compatible computer, and features a single interactive-graphics screen which displays all aspects of the design. Circuit elements, such as transmission lines, coupled lines, and lumped elements, are selected from a parts list and drawn on the screen using cursor keys. The circuit analysis is then performed directly from the screen drawing. To demonstrate the various features of Puff, predictions for a 10-GHz patch antenna with a stub matching circuit are compared with measurements made with an HP 8510 network analyzer