Realisation of ternary sigma-delta modulated arithmetic processing modules

Sigma-delta modulated systems have a number of very appealing properties and are, therefore, heavily used in analog to digital converters, amplifiers, and modulators. This paper presents new results which indicate that they may also have significant potential for general purpose arithmetic processing.

Digital signal processing

Signal Processing (SP) is a subject of central importance in engineering and the applied sciences. Signals are information-bearing functions, and SP deals with the analysis and processing of signals (by dedicated systems) to extract or modify information. Signal processing is necessary because signals normally contain information that is not readily usable or understandable, or which might be disturbed by unwanted sources such as noise. Although many signals are non-electrical, it is common to convert them into electrical signals for processing. Most natural signals (such as acoustic and biomedical signals) are continuous functions of time, with these signals being referred to as analog signals. Prior to the onset of digital computers, Analog Signal Processing (ASP) and analog systems were the only tool to deal with analog signals. Although ASP and analog systems are still widely used, Digital Signal Processing (DSP) and digital systems are attracting more attention, due in large part to the significant advantages of digital systems over the analog counterparts. These advantages include superiority in performance,s peed, reliability, efficiency of storage, size and cost. In addition, DSP can solve problems that cannot be solved using ASP, like the spectral analysis of multicomonent signals, adaptive filtering, and operations at very low frequencies. Following the recent developments in engineering which occurred in the 1980's and 1990's, DSP became one of the world's fastest growing industries. Since that time DSP has not only impacted on traditional areas of electrical engineering, but has had far reaching effects on other domains that deal with information such as economics, meteorology, seismology, bioengineering, oceanology, communications, astronomy, radar engineering, control engineering and various other applications. This book is based on the Lecture Notes of Associate Professor Zahir M. Hussain at RMIT University (Melbourne, 2001-2009), the research of Dr. Amin Z. Sadik (at QUT & RMIT, 2005-2008), and the Note of Professor Peter O'Shea at Queensland University of Technology. Part I of the book addresses the representation of analog and digital signals and systems in the time domain and in the frequency domain. The core topics covered are convolution, transforms (Fourier, Laplace, Z. Discrete-time Fourier, and Discrete Fourier), filters, and random signal analysis. There is also a treatment of some important applications of DSP, including signal detection in noise, radar range estimation, banking and financial applications, and audio effects production. Design and implementation of digital systems (such as integrators, differentiators, resonators and oscillators are also considered, along with the design of conventional digital filters. Part I is suitable for an elementary course in DSP. Part II (which is suitable for an advanced signal processing course), considers selected signal processing systems and techniques. Core topics covered are the Hilbert transformer, binary signal transmission, phase-locked loops, sigma-delta modulation, noise shaping, quantization, adaptive filters, and non-stationary signal analysis. Part III presents some selected advanced DSP topics. We hope that this book will contribute to the advancement of engineering education and that it will serve as a general reference book on digital signal processing.

The role of markup in the digital humanities

The digital humanities are growing rapidly in response to a rise in Internet use. What humanists mostly work on, and which forms much of the contents of our growing repositories, are digital surrogates of originally analog artefacts. But is the data model upon which many of those surrogates are based – embedded markup – adequate for the task? Or does it in fact inhibit reusability and flexibility? To enhance interoperability of resources and tools, some changes to the standard markup model are needed. Markup could be removed from the text and stored in standoff form. The versions of which many cultural heritage texts are composed could also be represented externally, and computed automatically. These changes would not disrupt existing data representations, which could be imported without significant data loss. They would also enhance automation and ease the increasing burden on the modern digital humanist.

Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(−)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT). The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch). In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (−)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT. Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

Relationships between appetite and quality of life in hemodialysis patients

The aim of this paper was to investigate the association between appetite and Kidney-Disease Specific Quality of Life in maintenance hemodialysis patients. Quality of Life (QoL) was measured using the Kidney Disease Quality Of Life survey. Appetite was measured using self-reported categories and a visual analog scale. Other nutritional parameters included Patient-Generated Subjective Global Assessment (PGSGA), dietary intake, body mass index and biochemical markers C-Reactive Protein and albumin. Even in this well nourished sample (n=62) of hemodialysis patients, PGSGA score (r=-0.629), subjective hunger sensations (r=0.420) and body mass index (r=-0.409) were all significantly associated with the Physical Health Domain of QoL. As self-reported appetite declined, QoL was significantly lower in nine domains which were mostly in the SF36 component and covered social functioning and physical domains. Appetite and other nutritional parameters were not as strongly associated with the Mental Health domain and Kidney Disease Component Summary Domains. Nutritional parameters, especially PGSGA score and appetite, appear to be important components of the physical health domain of QoL. As even small reductions in nutritional status were associated with significantly lower QoL scores, monitoring appetite and nutritional status is an important component of care for hemodialysis patients.

Network interactions and performance of a multi-function IEC 61850 process bus

New substation technology, such as non-conventional instrument transformers,and a need to reduce design and construction costs, are driving the adoption of Ethernet based digital process bus networks for high voltage substations. Protection and control applications can share a process bus, making more efficient use of the network infrastructure. This paper classifies and defines performance requirements for the protocols used in a process bus on the basis of application. These include GOOSE, SNMP and IEC 61850-9-2 sampled values. A method, based on the Multiple Spanning Tree Protocol (MSTP) and virtual local area networks, is presented that separates management and monitoring traffic from the rest of the process bus. A quantitative investigation of the interaction between various protocols used in a process bus is described. These tests also validate the effectiveness of the MSTP based traffic segregation method. While this paper focusses on a substation automation network, the results are applicable to other real-time industrial networks that implement multiple protocols. High volume sampled value data and time-critical circuit breaker tripping commands do not interact on a full duplex switched Ethernet network, even under very high network load conditions. This enables an efficient digital network to replace a large number of conventional analog connections between control rooms and high voltage switchyards.

A randomized controlled pilot study comparing aqueous cream with a beeswax and herbal oil cream in the provision of relief from postburn pruritis

Postburn itch is reported to affect up to 87% of the burn population. Although treatments for postburn itch are multimodal, they remain consistently ineffective. However, recent anecdotal evidence from several outpatients at a tertiary referral hospital suggests that a cream combining beeswax and several herbal oils may be effective in the minimization of postburn itch. The aim of this study was to test the efficacy of beeswax and herbal oil cream against the standard treatment of aqueous cream in the provision of relief from the symptoms of postburn itch. A randomized controlled trial compared two groups using a visual analog scale, frequency of cream application, itch recurrence after cream application, use of antipruritic medications, and sleep disturbance to determine the effect of itch severity and duration. Fifty-two participants were enrolled in the study (84% male) with a mean age of 35 years (SD = 16) and mean burn TBSA of 7.2% (SD = 7.7). Study results found that the beeswax and herbal oil cream reduce itch after application more frequently than aqueous cream (P = .001). In addition, when managed with beeswax and herbal oil cream, participants found that their itch recurred later (P ≤ .001) and their use of antipruritic medications was lower (P = .023). Findings of this study suggest beeswax and herbal oil cream to be more effective in the minimization of postburn itch than aqueous cream. Given this, a larger study examining the efficacy of beeswax and herbal oil cream appears warranted.

Digitally-implemented naturally sampled PWM suitable for multilevel converter control

For dynamic closed loop control of a multilevel converter with a low pulse number (ratio of switching frequency to synthesized fundamental), natural sampled pulse-width modulation (PWM) is the best form of modulation. Natural sampling does not introduce distortion or a delayed response to the modulating signal. However previous natural sampled PWM implementations have generally been analog. For a modular multilevel converter, a digital implementation has advantages of accuracy and flexibility. Re-sampled uniform PWM is a novel digital modulation technique which approaches the performance of natural PWM. Both hardware and software implementations for a five level multilevel converter phase are presented, demonstrating the improvement over uniform PWM.

Implementing natural PWM digitally

For dynamic closed loop control of a multilevel converter with a low switching frequency, natural sampled PWM is the best form of modulation. However previous natural sampled PWM implementations have generally been analog. A digital implementation has advantages, particularly for a multilevel converter. Re-sampled uniform PWM, a modulation technique which approaches the performance of natural PWM, is implemented both in software and hardware. Results demonstrating the improvement over uniformPWM techniques are presented.

Somatostatin, its receptors and analogs, in lung cancer

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [111In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer. Copyright © 2001 S. Karger AG, Basel.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

Raman and infrared spectroscopic characterization of the phosphate mineral Lithiophilite—LiMnPO4

The metal lithium is very important in industry, including lithium batteries. An important source of lithium besides continental brines is granitic pegmatites as in Australia. Lithiophilite is a lithium and manganese phosphate with chemical formula LiMnPO4 and forms a solid solution with triphylite, its Fe analog, and belongs to the triphylite group that includes karenwebberite, natrophilite, and sicklerite. The mineral lithiophilite was characterized by chemical analysis and spectroscopic techniques. The chemical is: Li1.01(Mn0.60, Fe0.41, Mg0.01, Ca0.01)(PO4)0.99 and corresponds to an intermediate member of the triphylite-lithiophilite series, with predominance of the lithiophilite member. The mineral lithiophilite is readily characterized by Raman and infrared spectroscopy.

Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis

As microenvironmental factors such as three-dimensionality and cell–matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to further our understanding of the PCa-bone crosstalk.