Simple locking of infrared and ultraviolet diode lasers to a visible laser using a LabVIEW proportional-integral-derivative controller on a Fabry-Perot signal.

Simultaneous laser locking of infrared (IR) and ultraviolet lasers to a visible stabilized reference laser is demonstrated via a Fabry-Perot (FP) cavity. LabVIEW is used to analyze the input, and an internal proportional-integral-derivative algorithm converts the FP signal to an analog locking feedback signal. The locking program stabilized both lasers to a long term stability of better than 9 MHz, with a custom-built IR laser undergoing significant improvement in frequency stabilization. The results of this study demonstrate the viability of a simple, computer-controlled, non-temperature-stabilized FP locking scheme for our applications, laser cooling of Ca(+) ions, and its use in other applications with similar modest frequency stabilization requirements.

CT colonography at low tube potential: using iterative reconstruction to decrease noise.

AIM: To determine the level of iterative reconstruction required to reduce increased image noise associated with low tube potential computed tomography (CT). MATERIALS AND METHODS: Fifty patients underwent CT colonography with a supine scan at 120 kVp and a prone scan at 100 kVp with other scan parameters unchanged. Both scans were reconstructed with filtered back projection (FBP) and increasing levels of adaptive statistical iterative reconstruction (ASiR) at 30%, 60%, and 90%. Mean noise, soft tissue and tagged fluid attenuation, contrast, and contrast-to-noise ratio (CNR) were collected from reconstructions at both 120 and 100 kVp and compared using a generalised linear mixed model. RESULTS: Decreasing tube potential from 120 to 100 kVp significantly increased image noise by 30-34% and tagged fluid attenuation by 120 HU at all ASiR levels (p<0.0001, all measures). Increasing ASiR from 0% (FBP) to 30%, 60%, and 90% resulted in significant decreases in noise and increases in CNR at both tube potentials (p<0.001, all comparisons). Compared to 120 kVp FBP, ASiR greater than 30% at 100 kVp yielded similar or lower image noise. CONCLUSIONS: Iterative reconstruction adequately compensates for increased image noise associated with low tube potential imaging while improving CNR. An ASiR level of approximately 50% at 100 kVp yields similar noise to 120 kVp without ASiR.

Off-resonance energy absorption in a linear Paul trap due to mass selective resonant quenching.

Linear Paul traps (LPT) are used in many experimental studies such as mass spectrometry, atom-ion collisions, and ion-molecule reactions. Mass selective resonant quenching (MSRQ) is implemented in LPT either to identify a charged particle's mass or to remove unwanted ions from a controlled experimental environment. In the latter case, MSRQ can introduce undesired heating to co-trapped ions of different mass, whose secular motion is off resonance with the quenching ac field, which we call off-resonance energy absorption (OREA). We present simulations and experimental evidence that show that the OREA increases exponentially with the number of ions loaded into the trap and with the amplitude of the off-resonance external ac field.

A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation.

Colorectal cancer represents the fourth commonest malignancy, and constitutes a major cause of significant morbidity and mortality among other diseases. However, the chemical therapy is still under development. Angiogenesis plays an important role in colon cancer development. We developed HMQ18-22 (a novel analog of taspine) with the aim to target angiogenesis. We found that HMQ18-22 significantly reduced angiogenesis of chicken chorioallantoic membrane (CAM) and mouse colon tissue, and inhibited cell migration and tube formation as well. Then, we verified the interaction between HMQ18-22 and VEGFR2 by AlphaScreen P-VEGFR assay, screened the targets on angiogenesis by VEGF Phospho Antibody Array, validated the target by western blot and RNAi in lovo cells. We found HMQ18-22 could decrease phosphorylation of VEGFR2(Tyr(1214)), VEGFR1(Tyr(1333)), Akt(Tyr(326)), protein kinase Cα (PKCα) (Tyr(657)) and phospholipase-Cγ-1 (PLCγ-1) (Tyr(771)). Most importantly, HMQ18-22 inhibited proliferation of lovo cell and tumor growth in a human colon tumor xenografted model of athymic mice. Compared with normal lovo cells proliferation, the inhibition on proliferation of knockdown cells (VEGFR2, VEGFR1, Akt, PKCα and PLCγ-1) by HMQ18-22 decreased. These results suggested that HMQ18-22 is a novel angiogenesis inhibitor and can be a useful therapeutic candidate for colon cancer intervention.

Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model.

AIMS: The pathogenesis of obesity remains incompletely understood. Drosophila have conserved neuroendocrine and digestion systems with human and become an excellent system for studying energy homeostasis. Here, we reported a novel obesity Drosophila model, in which expression of human protein, synphilin-1 (SP1), in neurons fosters positive energy balance. SUBJECTS AND METHODS: To further understand the actions of SP1 in energy balance control, the upstream activation sequence UAS/GAL4 system was used to generate human SP1 transgenic Drosophila. We characterized a human SP1 transgenic Drosophila by assessing SP1 expression, fat lipid deposition, food intake and fly locomotor activity to determine the major behavioral changes and their consequences in the development of the obesity-like phenotype. RESULTS: Overexpression of SP1 in neurons, but not peripheral cells, increased the body weight of flies compared with that of non-transgenic controls. SP1 increased food intake but did not affect locomotor activity. SP1 increased the levels of triacylglycerol, and the size of fat body cells and lipid droplets, indicating that SP1 increased lipid-fat disposition. Survival studies showed that SP1 transgenic flies were more resistant to food deprivation. SP1 regulated lipin gene expression that may participate in SP1-induced fat deposition and starvation resistance. CONCLUSION: These studies demonstrate that SP1 expression affects energy homeostasis in ways that enhance positive energy balance and provide a useful obesity model for future pathogenesis and therapeutic studies.

A novel obesity model: synphilin-1-induced hyperphagia and obesity in mice.

AIMS: The pathogenesis of obesity remains incompletely understood and the exploration of the role of novel proteins in obesity may provide important insights into its causes and treatments. Here, we report a previously unidentified role for synphilin-1 in the control of food intake and body weight. Synphilin-1, a cytoplasmic protein, was initially identified as an interaction partner of alpha-synuclein, and has implications in Parkinson's disease pathogenesis related to protein aggregation. SUBJECTS AND METHODS: To study the in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake and spontaneous activity to determine the major behavioral changes and their consequences in the development of the obesity phenotype. RESULTS: Expression of human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake, body weight and body fat. SP1 mice also displayed hyperinsulinemia, hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts consumed by non-transgenic mice prevented the increased body weight, adiposity, hyperinsulinemia and hyperleptinemia demonstrating that these were all the consequences of increased food intake. Transgenic expression of synphilin-1 was enriched in hypothalamic nuclei involved in feeding control, and fasting-induced elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin-1 is an important player in the hypothalamic energy balance regulatory system. CONCLUSION: These studies identify a novel function of synphilin-1 in controlling food intake and body weight, and may provide a unique obesity model for future studies of obesity pathogenesis and therapeutics.

Scan length optimization for pulmonary embolism at CT angiography: analysis based on the three-dimensional spatial distribution of 370 emboli in 100 patients.

AIM: To determine the size and three-dimensional spatial distribution of pulmonary emboli (PE) at computed tomography angiography (CTA) to optimize the scan length. MATERIALS AND METHODS: Two experienced radiologists jointly reviewed 100 consecutive, positive PE CTA studies performed in the Emergency Department (53 women; age 61±17 years). All studies were conducted on a 16-detector row CT machine. In each case, the number of emboli was counted and the proximal and distal spatial coordinates of each embolus documented. Coordinates of the main pulmonary artery bifurcation (MPAb) and carina were recorded. For normalization, the thoracic cavity height (H)-from inlet to lowest hemidiaphragm-was measured. The minimal scan lengths for (a) capturing all emboli and (b) rendering a positive diagnosis were determined. RESULTS: Three hundred and seventy (370) emboli were detected. The average number of PE per patient was 3.7 (maximum 12, minimum 1). Their average length was 2.7 cm. Nine patients had saddle emboli (9%), and 71% of emboli were at or below the MPAb. An 18 cm (0.90×H) scan length, centred 4 cm (0.18×H) below the carina, captures all PE in this dataset while reducing z-axis coverage by 29% (34% for normalized data). Moreover, a 14.2 cm (0.78×H) scan length appropriately centred captures at least one embolus in all patients while reducing coverage by 44% (43%). Decreasing scan length to the lesser of 14.2 cm and 0.78×H per patient reduces coverage by 47%. CONCLUSION: Scan length at CTA for PE can be reduced by up to 47% while preserving diagnostic accuracy for PE detection.

Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity.

Synphilin-1 is a cytoplasmic protein with unclear function. Synphilin-1 has been identified as an interaction partner of alpha-synuclein. The interaction between synphilin-1 and alpha-synuclein has implications in Parkinson's disease. In this study, we stably overexpressed human synphilin-1 in mouse N1E-115 neuroblastoma cells. We found that overexpression of synphilin-1 shortened cell growth doubling time and increased neurite outgrowth. Knockdown of endogenous synphilin-1 caused neuronal toxicity and shortened neurite outgrowth. We further found that synphilin-1 increased activation of the extracellular signal-regulated kinases (ERK1/2) and mediated neurite outgrowth. Rotenone, mitochondrial complex I inhibitor, has been shown previously to induce dopaminergic neurodegeneration and Parkinsonism in rats and Drosophila. We found that Rotenone induced apoptotic cell death in N1E-115 cells via caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of synphilin-1 significantly reduced Rotenone-induced cell death, caspase-3 activation and PARP cleavage. The results indicate that synphilin-1 displays trophic and protective effects in vitro, suggesting that synphilin-1 may play a protective role in Parkinson's disease (PD) pathogenesis and may lead to a potential therapeutic target for PD intervention.

Contrast-to-noise ratios of liver lesions using subtraction imaging on multiphase 64-detector row CT.

AIM: To measure contrast-to-noise ratios of liver lesions on conventional enhanced and digitally subtracted multidetector row computed tomography (CT) images. MATERIALS/METHODS: This study was approved by our hospital internal review board (IRB) and all collected data were evaluated in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. Subtracted datasets, using pixel-by-pixel subtraction of the post-contrast images from the pre-contrast images, were created from the 64 detector-row CT of patients undergoing three-phase examination of the liver (unenhanced, arterial phase, and portal venous phase). Regions of interest were used to calculate the contrast-to-noise ratios between the lesions and the background liver parenchyma on both the post-contrast and subtracted datasets using the following formula: (Lesion mean (HU) - Liver mean (HU))/standard deviation of mean outside patient (HU). These ratios were compared using a mixed linear statistical model. RESULTS: Contrast-to-noise ratios were calculated for 64 lesions in 50 consecutive patients. Of the 64 lesions, 42 were hypervascular and 22 were hypovascular. Subtracted datasets yielded statistically significant higher contrast-to-noise ratios of hypervascular lesions compared to normal liver parenchyma (p<0.0001). Subtraction did not yield a statistically significant improvement in contrast-to-noise ratios for hypovascular liver lesions (p=0.16). CONCLUSION: Post-processed subtraction CT images generate increased contrast-to-noise ratios for hypervascular liver lesions. As this technique is easy to perform and does not involve additional radiation exposure, it should be considered when evaluating for suspected hypervascular lesions.

Bacterial contamination associated with estuarine shoreline development.

AIMS: To examine the relationships among increasing estuarine shellfish closings due to bacterial contamination, adjacent shoreline land uses and environmental variables. METHODS AND RESULTS: A 1 year study of faecal coliform bacterial contamination of a small estuary in central NC, USA was done relative to adjacent land uses. The area has experienced rapid growth in residential shoreline development including the installation of adjacent, separate docking facilities for larger boats, each <11 slips (pseudomarina) that appear to be a single marina (individual facilities of >10 slips). Six near-shore sites were selected [old developed shore (OD), undeveloped shore (UD), two pseudomarinas (P1, P2), newly developed shore (ND) and a real marina (RM)]. Five locations were spaced along the shore near each site. Paired Thursday/Monday samples were collected biweekly (summer) and monthly (other seasons). Results indicate that OD had the highest bacteria counts followed by ND, RM and P1 & P2. Three sites (OD, ND and RM) failed to meet NC shellfishing waters standards at all locations. At the pseudomarina sites 4 of 10 locations failed to meet shellfish standards while two locations at UD failed to meet these standards. There were no significant differences between paired Thursday/Monday samples. At three sites (OD, UD and P2) bacteria counts were positively correlated with increased water level due to wind tides. CONCLUSIONS: Any type of estuarine shoreline development may result in closing of adjacent shellfishing waters. ND had bacterial counts second only to OD in spite of the retention of vegetated shoreline buffers and very new septic systems. As expected, the RM also failed to meet shellfish standards. Unexpectedly, only four of the 10 pseudomarina locations failed to meet the standards. Weekend boat use had no effect on bacterial counts. Surface runoff from rain and shoreline flooding from increased water levels increased bacterial counts, probably as a result of suspension of surface deposited faeces from wildlife and domestic animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Multiple docking facilities do not necessarily result in violations of shellfish water quality standards. However, the elevated bacterial counts observed along the newly developed shore suggest caution in approving the practice of allowing individual 'oyster gardening' off private piers if the oysters are intended for human consumption. The practice of automatic closure of shellfish waters around RMs was supported. Correlations of bacterial counts with time following significant rainfall suggests a sampling strategy to separate local sources of bacteria from more remote sources thus focusing limited remedial resources more effectively.

Radiofrequency ablation of bony metastatic disease.

Image-guided radiofrequency (RF) ablation is an emerging alternative therapy for treatment of cancer in patients who can not undergo surgical resection. We have performed RF ablation on patients to locally treat and palliate painful osseous metastatic disease for several years. We present an overview of various applications of RF ablation for treating osseous metastatic disease.

Multi-detector CT angiography of the intra-cranial circulation: normal anatomy and pathology with angiographic correlation.

Multidetector computed tomography angiography (MD-CTA) of the intra-cranial circulation shows great potential in the evaluation of intra-cranial vascular disease. Interpreting these studies requires a detailed knowledge of the technique, its advantages and disadvantages, as well as a strong understanding of normal intra-cranial vascular anatomy. The purpose of this review is to describe the technique for MD-CTA, demonstrate normal anatomy, anatomic variants and vascular pathology with an emphasis on aneurysms.

Early prostate cancer: is there a need for new treatment options?

Improvements in diagnostic techniques have led to prostate cancer being diagnosed in younger patients and at an earlier stage of disease. The question therefore arises as to what is the best treatment for early prostate cancer. The main issues to be considered are whether the cancer is likely to progress quicker if these patients do not receive early treatment and what the quality of life implications are for patients receiving early treatment. As yet, due to the lack of valid comparisons of treatments, there is no clear "best treatment" for early prostate cancer. A number of clinical trials, comparing current treatments or investigating potential new treatment options for early prostate cancer, are in progress. The results of these should clarify the relative benefits of currently available treatments. This article reviews the latest information on the incidence, prognosis and current treatments for early prostate cancer and discusses the need for new treatments. Potential clinical benefits and cost implications of new treatments for early prostate cancer, such as improved surgical and radiotherapy techniques and adjuvant medical therapy, are also evaluated.

CT of the duodenum: an overlooked segment gets its due.

Abdominal computed tomography (CT) is frequently performed to evaluate gastrointestinal pathologic conditions, and the majority of the gastrointestinal radiology literature has concentrated on the colon, stomach, and distal small bowel. In a description of CT findings of duodenal pathologic conditions, congenital, traumatic, inflammatory, and neoplastic diseases are presented. Congenital duodenal anomalies such as duplications and diverticula are usually asymptomatic, while annular pancreas and malrotation may manifest in the 1st decade of life. CT plays a vital role in the diagnosis of traumatic duodenal injury. Primary inflammatory processes of the duodenum such as ulcers and secondary involvement from pancreatitis can reliably be diagnosed at CT. Infectious diseases of the duodenum are difficult to diagnose, as the findings are not specific. While small bowel malignancies are relatively rare, lipoma, adenoma, and adenocarcinoma, as well as local extension from adjacent malignancies, can be diagnosed at CT. Careful CT technique and attention to the duodenum can result in reliable prospective diagnoses.

Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors.

SB-219383 and its analogues are a class of potent and specific inhibitors of bacterial tyrosyl-tRNA synthetases. Crystal structures of these inhibitors have been solved in complex with the tyrosyl-tRNA synthetase from Staphylococcus aureus, the bacterium that is largely responsible for hospital-acquired infections. The full-length enzyme yielded crystals that diffracted to 2.8 A resolution, but a truncated version of the enzyme allowed the resolution to be extended to 2.2 A. These inhibitors not only occupy the known substrate binding sites in unique ways, but also reveal a butyl binding pocket. It was reported that the Bacillus stearothermophilus TyrRS T51P mutant has much increased catalytic activity. The S. aureus enzyme happens to have a proline at position 51. Therefore, our structures may contribute to the understanding of the catalytic mechanism and provide the structural basis for designing novel antimicrobial agents.

State-of-the-art adrenal imaging.

The adrenal gland is a common site of disease, and detection of adrenal masses has increased with the expanding use of cross-sectional imaging. Radiology is playing a critical role in not only the detection of adrenal abnormalities but in characterizing them as benign or malignant. The purpose of the article is to illustrate and describe the appropriate radiologic work-up for diseases affecting the adrenal gland. The work-up of a suspected hyperfunctioning adrenal mass (pheochromocytoma and aldosteronoma) should start with appropriate biochemical screening tests followed by thin-collimation computed tomography (CT). If results of CT are not diagnostic, magnetic resonance (MR) and nuclear medicine imaging examinations should be performed. CT has become the study of choice to differentiate a benign adenoma from a metastasis in the oncology patient. If the attenuation of the adrenal gland is over 10 HU at nonenhanced CT, contrast material-enhanced CT should be performed and washout calculated. Over 50% washout of contrast material on a 10-minute delayed CT scan is diagnostic of an adenoma. For adrenal lesions that are indeterminate at CT in the oncology patient, chemical shift MR imaging or adrenal biopsy should be performed. Certain features can be used by the radiologist to establish a definitive diagnosis for most adrenal masses (including carcinoma, infections, and hemorrhage) based on imaging findings alone.