The ultrafast reactions in the photochromic cycle of water-soluble fulgimide photoswitches.

Photochromic switches are essential for the control and manipulation of nanoscale reactions and processes. The expansion of their application to aqueous environments depends strongly on the development of optimized water-soluble photoswitches. Here we present a femtosecond time-resolved investigation of the photochromic reactions (transition between the open and the closed form) of a water-soluble indolylfulgimide. We observe a pronounced effect of the protic nature of water as a solvent on the ultrafast ring-opening reaction. Typically, the excited state of the closed form has a larger dipole moment than the ground state, which leads to stabilization of the excited state in polar solvents and hence a lifetime (3 ps) longer than in non-polar solvents (2 ps). However, in water, despite the increased solvent polarity and the increased excited state dipole moment, the opposite trend for the excited state lifetime is observed (1.8 ps). This effect is caused by the opening of a new excited state deactivation pathway involving proton transfer reactions.

Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation.

There is little published long-term survival data for patients with colorectal liver metastases treated with radiofrequency ablation (RFA). We present a multivariate analysis of 5-year survival in 309 patients (198 male, aged 64 (24-92)) treated at 617 sessions. Our standard protocol used internally cooled electrodes introduced percutaneously under combined US and CT guidance/monitoring. The number and size of liver metastases, the presence and location of extrahepatic disease, primary resection, clinical, chemotherapy and follow-up data were recorded. Data analysis was performed using SPSS v.10. On multivariate analysis, significant survival factors were the presence of extrahepatic disease (p < 0.001) and liver tumour volume (p = 0.001). For 123 patients with five or less metastases of 5 cm or less maximum diameter and no extrahepatic disease median survival was 46 and 36 months from liver metastasis diagnosis and ablation, respectively; corresponding 3- and 5-year survival rates were 63%, 34% and 49%, 24%. Sixty-nine patients had three or less tumours of below 3.5 cm in diameter and their 5-year survival from ablation was 33%. There were 23/617(3.7%) local complications requiring intervention. Five-year survival of 24-33% post ablation in selected patients is superior to any published chemotherapy data and approaches the results of liver resection.

Deep Learning Classification of 3.5 GHz Band Spectrograms with Applications to Spectrum Sensing.

In the United States, the Federal Communications Commission has adopted rules permitting commercial wireless networks to share spectrum with federal incumbents in the 3.5 GHz Citizens Broadband Radio Service band. These rules require commercial systems to vacate the band when sensors detect radars operated by the U.S. military; a key example being the SPN-43 air traffic control radar. Such sensors require highly-accurate detection algorithms to meet their operating requirements. In this paper, using a library of over 14,000 3.5 GHz band spectrograms collected by a recent measurement campaign, we investigate the performance of thirteen methods for SPN-43 radar detection. Namely, we compare classical methods from signal detection theory and machine learning to several deep learning architectures. We demonstrate that machine learning algorithms appreciably outperform classical signal detection methods. Specifically, we find that a three-layer convolutional neural network offers a superior tradeoff between accuracy and computational complexity. Last, we apply this three-layer network to generate descriptive statistics for the full 3.5 GHz spectrogram library. Our findings highlight potential weaknesses of classical methods and strengths of modern machine learning algorithms for radar detection in the 3.5 GHz band.

Cathepsin D from the liver of the antarctic icefish Chionodraco hamatus exhibits unusual activity and stability at high temperatures1.

Cathepsin D was purified to homogeneity from the liver of Antarctic icefish by anion-exchange chromatography followed by affinity chromatography on concanavalin-A Sepharose. The purified enzyme showed a molecular mass of 40 kDa and displayed optimal activity at pH 3.0 with a synthetic chromogenic substrate. The N-terminal sequence of this proteinase was determined by automated Edman degradation and was used to design a primer for use in reverse-transcriptase polymerase chain reaction. The open reading frame of the cloned cDNA encoded an aspartic proteinase, which contained the experimentally determined N-terminal sequence. The predicted sequence (396 residues) had a high similarity with those of cathepsin D from various vertebrate sources, but was considerably different from that of nothepsin, a distinct aspartic proteinase described previously from Antarctic fish [1]. Determination of kinetic parameters for substrate hydrolysis showed that, at temperatures between 8 and 50 degrees C, the icefish cathepsin D had a higher specificity constant (kcat/Km) than human cathepsin D. The stability of both enzymes was measured at 50 degrees C and half-lives of 55 and 3 min were derived for icefish and human cathepsin D, respectively.

The versatility of phosphoenolpyruvate and its vinyl ether products in biosynthesis.

The diverse enzymes that use phosphoenolpyruvate as a substrate lie at the heart of cellular energy metabolism, as well as a number of critical biosynthetic pathways. The versatility of the enol ether linkage is reflected not only in the rich chemistry and enzymology of PEP, but also in the variety of metabolites in which the high-energy enol ether linkage is preserved.

Cloning, expression and characterisation of murine procathepsin E.

The cDNA encoding murine procathepsin E was isolated and sequenced and recombinant enzyme was produced in Escherichia coli. The activity of the purified recombinant mouse cathepsin E was characterised quantitatively using two synthetic peptide substrates and naturally occurring inhibitors. The majority of the recombinant enzyme was present as a homodimer (Mr approximately 80) in which the two monomers were linked by an intermolecular disulfide bond. By analogy to previous studies with human cathepsin E, this is most likely a consequence of the presence of a unique cysteine residue near the N-terminus of the mature proteinase. The availability of (i) recombinant murine enzyme in reasonable quantities and (ii) a full-length cDNA now enables structural investigations and attempts to generate 'knock-out' mice deficient in this important aspartic proteinase to be undertaken.

Generation of human endothelin by cathepsin E.

Highly-purified cathepsin D processed human big endothelin1-38 into endothelin-like fragments but did not appear to generate endothelin1-21 under the conditions employed. By contrast, human cathepsin E specifically cleaved human big endothelin into endothelin1-21 and the C-terminal fragment under identical conditions but did not degrade either product further.

Non-invasive screening for renal artery stenosis with ultrasound contrast enhancement.

OBJECTIVE: Our aim was to evaluate duplex ultrasound imaging in the identification of renal artery stenosis using a new technique to enhance the recorded Doppler signal. DESIGN: Colour Doppler studies of interlobar renal arteries were performed before and after enhancement using an intravenous contrast of galactose microparticle suspension containing microbubbles (Levovist, Schering) in patients with angiographically confirmed renal artery stenosis. SETTING: Blood Pressure Unit, St. George's Hospital Medical School, and Department of Radiology. The Middlesex Hospital, London, UK. PARTICIPANTS: Twenty-one consecutive hypertensive patients in whom the diagnosis of renal artery stenosis was made on digital subtraction angiography. MAIN OUTCOME MEASURES: The diagnosis of haemodynamically significant renal artery stenosis (> or = 60% on angiography). RESULTS: With Levovist, there was a 20 db increase in the Doppler intensity and, as a result, intrarenal signals were much more clearly delineated and distinct spectral waveforms were obtained from all but one kidney, which was occluded. Significant associations were found between the degree of stenosis (as assessed by angiography) and the following Doppler parameters: diastolic velocity (F = 7.6; P < 0.01), acceleration time (F = 33.5, < 0.0001), peak systolic velocity (F = 37.7, P < 0.0001) and acceleration (F = 60.0; P < 0.0001). Without enhancement, there were five false-positive and two false-negative examinations (sensitivity 85%; specificity 79%) using the acceleration cut-off value of 3.5 m/s2 to identify haemodynamically significant renal artery stenosis (> or = 60% on angiography). After contrast enhancement, there were only three false-positive and one false-negative examinations (sensitivity 94% and specificity of 88%) using the acceleration cut-off value of 3.75 m/s2 and the examination time was reduced by approximately half (sensitivity and specificity of 90% using the acceleration cut-off value of 3.5 m/s2). CONCLUSIONS: Our results suggest that renal duplex scanning using contrast enhancement is a promising new non-invasive technique in screening patients with suspected renal artery stenosis. Contrast enhancement produces more reproducible spectral waveforms, improves accuracy and halves the examination time.

Polyacrylamides bearing pendant alpha-sialoside groups strongly inhibit agglutination of erythrocytes by influenza A virus: multivalency and steric stabilization of particulate biological systems.

An alpha-sialoside linked to acrylamide by a short connector (5-acetamido-2-O-(N-acryloyl-8-amino-5-oxaoctyl)-2,6-anhydro-3,5-d ideoxy-D-galacto-alpha-nonulopyranosonoic acid, 1) was prepared. Compound 1 formed high molecular weight copolymers with acrylamide, derivatives of acrylamide, and/or vinylpyrrolidone upon photochemically-initiated free radical polymerization. Those copolymers for which the substituents on the acrylamido nitrogen were small inhibited the agglutination of chicken erythrocytes induced by influenza virus (X-31 (H3N2); a recombinant strain of A/Aichi/2/68 (H3N2) and A/Puerto Rico/8/34 grown in chicken eggs). The inhibitory power of the polymers depended strongly on the conditions of polymerization and the sialic acid content of the polymer. The strongest inhibitors were copolymers (poly(1-co-acrylamide)) formed from mixtures of monomer containing [1]/([1] + [acrylamide]) approximately 0.2-0.7; these copolymers inhibited hemagglutination 10(4)-10(5) times more strongly than did similar concentrations of alpha-methyl sialoside (calculated on the basis of the total concentration of individual sialic acid groups in the solution, whether attached to polymer or present as monomers). Samples polymerized in the presence of low concentrations of cross-linking reagents (bis(acrylamido)methane, BIS, and 2,2'-bis(acrylamido)ethyl disulfide, BAC) also showed increased inhibition (10-10(3)-fold relative to monomers), but their use was limited by their poor solubility. Sterically demanding substituents on any position of the acrylamide component (substituents attached to the vinyl group or N-alkyl groups that are larger than hydroxyethyl) reduced the inhibitory power of the polymer. A 1H NMR assay and a fluorescence depolarization assay showed that poly(1-co-acrylamide) bound to a solubilized trimeric form of the viral receptor for sialic acid (bromelain cleaved hemagglutinin, BHA), less tightly than 1, on a per sialic acid basis. A similar result was also obtained with a model system comprising lactic dehydrogenase (a tetramer) and polymeric derivatives of oxamic acid: that is, poly((28, 29, 30, or 31)-co-acrylamide) had a higher inhibition constant for tetrameric lactic dehydrogenase than did the corresponding monomers (28, 29, 30, or 31) on a per oxamate basis. Poly(1-co-acrylamide) is, in principle, capable of inhibiting the agglutination of erythrocytes by several mechanisms: (1) entropically enhanced binding of the polymer (acting as a polyvalent inhibitor) to the surface of the virus; (2) steric interference of the approach of the virus to the surface of the erythrocyte by a water-swollen layer of the polymer on the surface of the virus; (3) aggregation of the virus induced by the polymer.(ABSTRACT TRUNCATED AT 400 WORDS)

Computed tomography-pathologic assessment of laser-induced necrosis in rat liver.

RATIONALE AND OBJECTIVES: Interstitial laser photocoagulation (ILP) causes localized tissue necrosis. This study was performed to determine 1) whether the changes seen on computed tomography (CT) correspond to the necrosis pathologically, and 2) which CT technique best shows the necrosis. METHODS: Eighteen Wistar rats had ILP to their liver using a neodymium yttrium aluminum garnet [Nd:YAG] laser. Radio-opaque markers attached to the liver defined an imaging plane. Precontrast "dynamic" and delayed CT scans were performed. The size of necrosis was measured on CT, and macroscopically after resecting the liver. Computed tomography density numbers were measured from the necrotic area and normal liver for each CT technique. RESULTS: There was a good correlation between the necrosis size on CT and pathologically (P < .001). Maximum lesion-to-liver contrast was obtained on "dynamic" CT scans. CONCLUSIONS: The extent of tissue density changes on CT in rat liver after ILP match the extent of necrosis seen pathologically. The best CT technique use assessed for evaluating laser-induced liver necrosis is dynamic contrast-enhanced scanning.

Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies.

We studied 24 male patients aged 26-62 years (median 41) prospectively presenting over a 5 year period with clinical features of hypogonadism and erectile dysfunction (ED), who had been treated with autologous or allogeneic bone marrow/stem cell transplant for a variety of haematological malignancies and had received either high-dose chemotherapy or high-dose chemotherapy combined with total body irradiation (TBI). Ten healthy adult controls (aged 35-50 years) were also studied. Erectile dysfunction (ED) was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume including orchidometry, FSH, LH and testosterone measurements. Libido and ejaculatory function were also recorded. Patients had severe hypogonadism as evidenced by low mean testicular volume (7.0 +/- 2.4 ml vs 20 +/- 2.0 ml; P < 0.001), elevated gonadotrophins (FSH = 18.54 +/- 7.61 vs 5 IU/l (P < 0.001); LH = 8.02 +/- 2.89 vs 3. 9 IU/l (P < 0.001)) and low normal mean testosterone levels (16.4 nmol/l +/- 9.1 vs 22.4 nmol/l (P < 0.5)). Cavernosal arterial insufficiency was found in 11/14 of TBI-treated and in 3/10 HDC-treated patients, indicative of vasculogenic damage to corpora cavernosal vessels. Patients were given a therapeutic trial with testosterone replacement therapy (TRT). Those who had diminished libido had a marked improvement in their symptoms but the effect of TRT on ED was equivocal. In conclusion, this is the first report to show vasculogenic insufficiency in patients with haematological malignancies treated by BMT. Although hypogonadism can account for diminished libido, arteriogenic insufficiency is likely to be an important factor accounting for ED in these patients, especially those treated by TBI. We recommend a comprehensive assessment including endocrine profile and colour flow Doppler study in formulating the best management plan in recipients of high-dose therapy presenting after transplant with ED.

Percutaneous fine needle aspiration cytology of the pancreas: advantages and pitfalls.

Fine needle aspiration of the pancreas was performed in 62 patients with radiological suspicion of malignancy. All fine needle aspirates were taken under computed tomography or ultrasound guidance. Fine needle aspirates were positive in 31 of 41 patients with histologically or clinically confirmed pancreatic carcinoma. There were no false positive results. The sensitivity of this method for detecting malignant disease was 86%. Cytology was not able to provide conclusive results of benign conditions. Difficulties were encountered in diagnosing well differentiated carcinoma and neuroendocrine tumours and distinguishing them from reactive epithelium and islet cell hyperplasia, respectively. This resulted in a 12.1% false negative rate. There were no complications in our series. Percutaneous fine needle aspiration proved a reliable method of diagnosing pancreatic carcinoma.

Role of immunoblotting in the diagnosis of culture negative and enterococcal endocarditis.

Serum samples from patients with endocarditis and septicaemia due to Enterococcus faecalis, Enterococcus faecium, Streptococcus bovis, and Streptococcus sanguis were immunoblotted against antigenic extracts from all four species. In E faecalis endocarditis there was a strong IgM response to E faecalis antigenic bands of 112, 88-90, and 45-47 Kd and a strong IgG response to 88-90 and 45-47 Kd bands. In E faecium endocarditis there was a pronounced IgG response to an E faecium band of 82-90 Kd. For S bovis endocarditis, there was a strong IgG response to several components of S bovis including bands of 66, 58, 52 and 4 Kd. For S sanguis, there was a strong IgG response to bands of 80-82, 76, 60 and 45 Kd. These patterns of antibody production were absent in patients with uncomplicated septicaemia and in controls. The delineation of these patterns enabled confirmation of the final diagnosis in seven patients initially suspected of having culture negative endocarditis.

Pancreatic duct dilatation after secretin stimulation in patients with pancreas divisum.

Pancreas divisum is the most common anatomical variant of pancreatic ductal anatomy. It has been suggested that obstruction at the accessory papilla in subjects with pancreas divisum can be assessed by measurement of ductal diameter by ultrasonic examination after a maximal secretory stimulus with i.v. secretin. We have prospectively assessed this test in 44 individuals; nine healthy controls, nine patients with abdominal pain and normal pancreatic anatomy, 17 patients with pancreas divisum and abdominal pain but no other evidence of pancreatitis, and nine patients with pancreas divisum and either chronic or recurrent acute pancreatitis. We have found no correlation between ductal anatomy and response to i.v. secretin. Secretin provocation tests do not indicate which patients have accessory papillary stenosis and do not add support to the hypothesis of obstruction leading to pancreatitis in patients with pancreas divisum.

Radiofrequency ablation extends the scope of surgery in colorectal liver metastases.

AIMS: To assess outcome in patients treated by a multidisciplinary team, with a combination of liver resection and RF ablation. METHODS: Sixteen unselected patients (f=9; m=7) with colorectal liver metastases who were not suitable for surgery alone, were treated as follows: six had RF ablation at open laparotomy, three patients had synchronous ablation and resection while seven patients had RF ablation after liver resection. Standard liver resection techniques were used. RF was performed using internally cooled, single or cluster electrodes with a high power (200 W) generator. All patients were followed with regular contrast enhanced CT and survival noted. RESULTS: A total of 27 tumours with diameters 1.2-10 cm were treated. Two minor complications were recorded. 2/6 (33%) who had intraoperative RF had incomplete ablation due to large tumour size (6 and 10 cm respectively). Further RF ablation sessions were carried out successfully. 11/16 (69%) are alive at 2 years of whom 7 (44%) have no evidence of residual or recurrent liver disease. CONCLUSION: In our study, RF ablation extends the therapeutic envelope, is an effective local treatment of liver metastases and improves life expectancy.

Recent developments in biliary tract imaging.

Recent imaging innovations and their role in patient management are discussed in this article. Additional topics include the place of endoscopic ultrasound (echoendoscopic and miniprobe), the impact of spiral CT, new developments in MR imaging, and a review of noninvasive cholangiography--CT scans and MR imaging.

Fetal echocardiography in three and four dimensions.

A three-dimensional (3D) acquisition system using an electromagnetic position sensor attached to a standard transducer on an unmodified ultrasound scanner was developed to capture two-dimensional (2D)-fetal echocardiograms at various positions and orientations. Operating in real-time directed M-mode allowed recording of 2D structural images and cardiac motion curves, from which the fetal cardiac phase could be determined. By digitising over 100 image frames for each scanning sequence, and by selecting frames at particular phases, 3D views of the fetal heart were reconstructed for each phase. Of 20 sequences of six fetuses scanned, 13 sequences successfully demonstrated usable 3D fetal heart structures, including four cardiac chambers, ventricular and atrial septa, foramen ovale and some of the cardiac valves and great vessels. Rearrangement of those phased 3D images into a cyclic sequence could generate dynamic 3D views of a beating fetal heart. We believe that, with further technical development, this new approach will be of use in the diagnosis of prenatal cardiac malformations and malfunctions, in in utero cardiac surgery and in fetal cardiology teaching.

Simultaneous use of two ultrasound scanners for motion-gated three-dimensional fetal echocardiography.

The aim of this study was to determine whether or not simultaneous use of an additional Doppler transducer could provide sufficient cardiovascular motion information without significantly interfering with three-dimensional (3-D) cardiac structural data acquisition by a primary two-dimensional (2-D) transducer. To determine sources of interference, paired transducers were activated alternatively and simultaneously in and out of a water bath, with and without electrical insulating and electromagnetic shielding. To determine factors affecting interference, pairs were tested on a phantom with different separating distances and angles between paired ultrasound (US) beams and under different 2-D depths and Doppler scales. Results show that the dominant source of interference is acoustic cross talk. The severity was mainly affected by transducer pairing and by separating distances and angles, and the pattern by display settings. With optimised settings, sufficient structural and motion data were obtained simultaneously in 9 of 12 fetal hearts, and detailed 3-D views could be reconstructed free of motion artefacts, confirming the feasibility of using the method for motion-gated 3-D fetal cardiac imaging. New scanner design strategy was then proposed.

Online motion-gated dynamic three-dimensional echocardiography in the fetus--preliminary results.

The aim of this study was to visualise the fetal heart in dynamic three dimensions (4-D) during an ultrasound (US) scan (online), rather than after (offline). With special pairing and sequential setting to minimise interference between two scanners, umbilical arterial Doppler waveforms (UADWs) from one scanner were used as an online motion gating source to trigger simultaneous 3-D cardiac structural data acquisition by another. Of 25 data sets from 10 fetuses, 18 were acquired in 15 to 30 s per set with > or = 50% Doppler waveforms efficiently converted to triggering signals. Of 15 valid 4-D data sets, 10 were reconstructed in 2 to 20 min, compared to over 2 h previously reported (mainly for offline gating). Fine structures (including chordae tendinae and trabecular muscles) were depicted in six sets. The main problems in degrading 4-D images were extensive shadowing (6) from bony structures during rigid mechanical scanning, and random motion artefacts (6) from prolonged setting-up time with a complex combination of several systems. Integration of these systems is, therefore, recommended.

Conversion of umbilical arterial Doppler waveforms to cardiac cycle triggering signals: a preparatory study for online motion-gated three-dimensional fetal echocardiography.

To remove motion artefacts, a device was built to convert "noisy" umbilical arterial Doppler waveforms (UADWs) from an ultrasound (US) system into sharp ECG R-wave-like cardiac cycle triggering signals (CCTSs). These CCTSs were then used to gate a simultaneous (online) 3-D acquisition of sectional fetal echocardiograms from another US system. To test the conversion performance, a study was carried out in sheep fetal twins. Pulmonary arterial flow waveforms (PAFWs) from implanted probes were traced, in the meantime, to determine the reference cardiac cycle. Interference caused by running the two nonsynchronised US systems was controlled to three degrees (not-noticeable, moderate, and severe), together with high (> or = 40 cm/s) and low (< 40) flow velocities on UADWs. The conversion efficiency, assessed by the percentage of UADWs converted into CCTSs, was in the range of 83% to 100% for not-noticeable and moderate interference, and 0% to 71% for severe interference. The triggering accuracy, assessed by [(time lag mean between the onsets of PAFWs and corresponding CCTSs) -- (its 99% confidence level)] / the mean, was 90% to 96% for the not-noticeable interference high- and low-flow groups and for the moderate interference high-flow group; 19% to 93% for the moderate interference low-flow group; and from not obtainable up to 90% for the severe interference groups. The results show that UADWs can be used as a satisfactory online motion-gating source even in the presence of moderate interference. The major problems are from severe interference or moderate interference with low-flow velocity, which can be minimised/eliminated by the integration of the individual systems involved.