Scattering parameter measurements and amplifier design

The scattering parameter formulation in describing the small-signal operation of an active two-port device is developed. The inherent advantages of measuring the scattering parameters at UHF frequencies and the clear insight into the design problem are demonstrated. Some of the practical difficulties in a typical design problem are also considered --Abstract, page ii

Remote Detection of Acoustic Boundaries Using Radiation Imaging Operators

In this paper, we present an acoustic imaging operator. This operator is based upon combining the material boundary conditions at an acoustic boundary and the radiation boundary conditions associated with one way wave propagation. Numerical examples, using the second-order imaging operator, are presented in order to demonstrate the applicability of this method to the detection of two-dimensional boundaries

Treatment Toxicity: Radiation

Radiation exposures, both intentional and unintentional, have influence on normal tissue function. Short-term and long-term injuries can occur to all cell systems of both limited and rapid self-renewal potential. Radiation effects can last a lifetime for a patient and can produce complications for all organs and systems. Often invisible at the time of exposure, the fingerprints for cell damage can appear at any timepoint after. Health-care providers will need comprehensive knowledge and understanding of the acute and late effects of radiation exposure and how these interrelate with immediate and long-term care

Proton Therapy Center Layout and Interface

Due to space requirements and a substantial financial burden, the feasibility of health systems adopting proton therapy has been called into question. However, advances in facility design and treatment delivery have allowed institutions offering proton therapy to reduce footprint while incorporating technological improvements at reduced costs. As the number of centers and patients treated continue to increase, this chapter will review the layout and interface of proton therapy facilities providing a detailed overview of the design, costs and faculty and staff considerations

Volcanic and Tectonic Constraints on the Evolution of Venus

Surface geologic features form a detailed record of Venus’ evolution. Venus displays a profusion of volcanic and tectonics features, including both familiar and exotic forms. One challenge to assessing the role of these features in Venus’ evolution is that there are too few impact craters to permit age dates for specific features or regions. Similarly, without surface water, erosion is limited and cannot be used to evaluate age. These same observations indicate Venus has, on average, a very young surface (150–1000 Ma), with the most recent surface deformation and volcanism largely preserved on the surface except where covered by limited impact ejecta. In contrast, most geologic activity on Mars, the Moon, and Mercury occurred in the 1st billion years. Earth’s geologic processes are almost all a result of plate tectonics. Venus’ lacks such a network of connected, large scale plates, leaving the nature of Venus’ dominant geodynamic process up for debate. In this review article, we describe Venus’ key volcanic and tectonic features, models for their origin, and possible links to evolution. We also present current knowledge of the composition and thickness of the crust, lithospheric thickness, and heat flow given their critical role in shaping surface geology and interior evolution. Given Venus’ hot lithosphere, abundant activity and potential analogues of continents, roll-back subduction, and microplates, it may provide insights into early Earth, prior to the onset of true plate tectonics. We explore similarities and differences between Venus and the Proterozoic or Archean Earth. Finally, we describe the future measurements needed to advance our understanding of volcanism, tectonism, and the evolution of Venus

Digitization workflows for flat sheets and packets of plants, algae, and fungi

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141708/1/aps31500065.pd

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain

Loss of the Urothelial Differentiation Marker FOXA1 Is Associated with High Grade, Late Stage Bladder Cancer and Increased Tumor Proliferation

Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001), and loss of FOXA1 is associated with high histologic grade (p<0.001). Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC) exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes of MIBC and urothelial cell proliferation, and suggest an important role for FOXA1 in the malignant phenotype of MIBC

Tumor Transcriptome Sequencing Reveals Allelic Expression Imbalances Associated with Copy Number Alterations

Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor