Direct observation of vortices in an electron fluid.

Vortices are the hallmarks of hydrodynamic flow. Strongly interacting electrons in ultrapure conductors can display signatures of hydrodynamic behaviour, including negative non-local resistance1-4, higher-than-ballistic conduction5-7, Poiseuille flow in narrow channels8-10 and violation of the Wiedemann-Franz law11. Here we provide a visualization of whirlpools in an electron fluid. By using a nanoscale scanning superconducting quantum interference device on a tip12, we image the current distribution in a circular chamber connected through a small aperture to a current-carrying strip in the high-purity type II Weyl semimetal WTe2. In this geometry, the Gurzhi momentum diffusion length and the size of the aperture determine the vortex stability phase diagram. We find that vortices are present for only small apertures, whereas the flow is laminar (non-vortical) for larger apertures. Near the vortical-to-laminar transition, we observe the single vortex in the chamber splitting into two vortices; this behaviour is expected only in the hydrodynamic regime and is not anticipated for ballistic transport. These findings suggest a new mechanism of hydrodynamic flow in thin pure crystals such that the spatial diffusion of electron momenta is enabled by small-angle scattering at the surfaces instead of the routinely invoked electron-electron scattering, which becomes extremely weak at low temperatures. This surface-induced para-hydrodynamics, which mimics many aspects of conventional hydrodynamics including vortices, opens new possibilities for exploring and using electron fluidics in high-mobility electron systems.

Rationale and design of the Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE): interim analysis at 30 days of the first 180 patients enrolled.

AIM: The Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE) is a long-term 1200-patient multicenter prospective study initiated to augment the knowledge base (poolable and comparable) about endovascular aortic repair (EVAR) in a real-world population implanted with a single latest-generation stent graft system (Endurant). With enrollment ongoing at 80 high-volume sites, the registry has limited inclusion/exclusion criteria or procedural specification. Technical and clinical data will be reported through 5 years. METHODS: An interim analysis was performed on investigator-reported data for the first 180 patients enrolled. These patients were asymptomatic elderly males (92.1%) with considerable comorbidities. For 47.3% of the patients, the American Society of Anesthesiologists risk class was either III or IV. The Endurant stent graft was successfully deployed in 99.4% of patients for elective treatment of abdominal aortic aneurysm. RESULTS: Through 30 days, the rate of all-cause mortality was 1.7% (N=3), with all 3 deaths classified as procedure-related but not device-related. The rate of secondary endovascular procedures was 1.1%, and the rate of conversion to open repair was 0.6%. At postprocedure and at 30-day follow-up, there were no type I or type III endoleaks and no instances of stent graft kinking, thrombosis, or occlusion. ENGAGE represents the largest real-world registry for any single EVAR stent graft. CONCLUSION: The interim results through 30 days of the first 180 patients enrolled are promising. Longer-term follow-up for more patients will be reported.

Molecular characterization of the plant virus genus Ourmiavirus and evidence of inter-kingdom reassortment of viral genome segments as its possible route of origin.

Ourmia melon virus (OuMV), Epirus cherry virus (EpCV) and Cassava virus C (CsVC) are three species placed in the genus Ourmiavirus. We cloned and sequenced their RNA genomes. The sizes of the three genomic RNAs of OuMV, the type member of the genus, were 2814, 1064 and 974 nt and each had one open reading frame. RNA1 potentially encoded a 97.5 kDa protein carrying the GDD motif typical of RNA-dependent RNA polymerases (RdRps). The putative RdRps of ourmiaviruses are distantly related to known viral RdRps, with the closest similarity and phylogenetic affinity observed with fungal viruses of the genus Narnaviridae. RNA2 encoded a 31.6 kDa protein which, expressed in bacteria as a His-tag fusion protein and in plants through agroinfiltration, reacted specifically with antibodies made against tubular structures found in the cytoplasm. The ORF2 product is significantly similar to movement proteins of the genus Tombusviridae, and phylogenetic analysis supported this evolutionary relationship. The product of OuMV ORF3 is a 23.8 kDa protein. This protein was also expressed in bacteria and plants, and reacted specifically with antisera against the OuMV coat protein. The sequence of the ORF3 protein showed limited but significant similarity to capsid proteins of several plant and animal viruses, although phylogenetic analysis failed to reveal its most likely origin. Taken together, these results indicate that ourmiaviruses comprise a unique group of plant viruses that might have evolved by reassortment of genomic segments of RNA viruses infecting hosts belonging to different eukaryotic kingdoms, in particular, fungi and plants.

Genome of the extremely radiation-resistant bacterium Deinococcus radiodurans viewed from the perspective of comparative genomics.

The bacterium Deinococcus radiodurans shows remarkable resistance to a range of damage caused by ionizing radiation, desiccation, UV radiation, oxidizing agents, and electrophilic mutagens. D. radiodurans is best known for its extreme resistance to ionizing radiation; not only can it grow continuously in the presence of chronic radiation (6 kilorads/h), but also it can survive acute exposures to gamma radiation exceeding 1,500 kilorads without dying or undergoing induced mutation. These characteristics were the impetus for sequencing the genome of D. radiodurans and the ongoing development of its use for bioremediation of radioactive wastes. Although it is known that these multiple resistance phenotypes stem from efficient DNA repair processes, the mechanisms underlying these extraordinary repair capabilities remain poorly understood. In this work we present an extensive comparative sequence analysis of the Deinococcus genome. Deinococcus is the first representative with a completely sequenced genome from a distinct bacterial lineage of extremophiles, the Thermus-Deinococcus group. Phylogenetic tree analysis, combined with the identification of several synapomorphies between Thermus and Deinococcus, supports the hypothesis that it is an ancient group with no clear affinities to any of the other known bacterial lineages. Distinctive features of the Deinococcus genome as well as features shared with other free-living bacteria were revealed by comparison of its proteome to the collection of clusters of orthologous groups of proteins. Analysis of paralogs in Deinococcus has revealed several unique protein families. In addition, specific expansions of several other families including phosphatases, proteases, acyltransferases, and Nudix family pyrophosphohydrolases were detected. Genes that potentially affect DNA repair and recombination and stress responses were investigated in detail. Some proteins appear to have been horizontally transferred from eukaryotes and are not present in other bacteria. For example, three proteins homologous to plant desiccation resistance proteins were identified, and these are particularly interesting because of the correlation between desiccation and radiation resistance. Compared to other bacteria, the D. radiodurans genome is enriched in repetitive sequences, namely, IS-like transposons and small intergenic repeats. In combination, these observations suggest that several different biological mechanisms contribute to the multiple DNA repair-dependent phenotypes of this organism.

Origin of an animal mitochondrial DNA polymerase subunit via lineage-specific acquisition of a glycyl-tRNA synthetase from bacteria of the Thermus-Deinococcus group.

Phylogenetic tree analysis shows that the accessory subunit animal mitochondrial DNA polymerase emerges as a result of horizontal transfer of the gene encoding glycyl-tRNA synthetase from a bacterium of the Thermus-Deinococcus group into the animal nuclear genome. This acquisition by a distinct eukaryotic lineage of a gene encoding a mitochondrial protein from a nonmitochondrial bacterial source underscores the contribution of different types of horizontal transfer event to the evolution of eukaryotes.

Gene conversions in genes encoding outer-membrane proteins in H. pylori and C. pneumoniae.

Helicobacter pylori and Chlamydia pneumoniae are both pathogenic to humans. Their genomes have recently been completed, allowing detailed study of their evolution and organization. Here we describe an evolutionary analysis of the H. pylori and C. pneumoniae genes that encode their outer-membrane proteins. By comparing complete genome sequences of two H. pylori strains and two C. pneumoniae strains, we identify multiple independent conversions among these genes. Such recombination events might provide a selective advantage for these bacterial pathogens.

Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model.

Intimal hyperplasia is induced by therapeutic vascular interventions and often results in clinically important narrowing of the vascular lumen. Examination of the role of TGF-beta 1 in a rat carotid artery injury model confirmed the presence of a previously reported increase in TGF-beta 1 mRNA in the media of injured arteries. Administration of neutralizing anti- TGF-beta 1 antibodies significantly (P < 0.05) reduced the size of the intimal lesions that developed after carotid balloon injury. A control antibody had no effect. The intimal/medial area ratio was also reduced in the anti-TGF-beta 1 group relative to controls (P < 0.01). Immunohistochemical staining showed that two TGF-beta 1-induced extracellular matrix components, EDA + fibronectin and versican, were greatly increased in the untreated neointimal lesions, but were almost completely absent from the lesions of the anti-TGF-beta 1-treated animals. We conclude that TGF-beta 1 is causally involved in the development of intimal hyperplasia, and that anti-TGF-beta 1 agents may be useful in achieving at least partial control of this condition.

Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements.

PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been annotated by human experts, and a popular measure of retrieval accuracy (ROC) that can be normalized to take on values between 0 (worst) and 1 (best). The modifications we consider novel improve the ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the benefits from four modifications we included in the 'baseline' version, even though they were not implemented in PSI-BLAST version 2.0. The improvement in accuracy was confirmed on a small second test set. This test involved analyzing three protein families with curated lists of true positives from the non-redundant protein database. The modification that accounts for the majority of the improvement is the use, for each database sequence, of a position-specific scoring system tuned to that sequence's amino acid composition. The use of composition-based statistics is particularly beneficial for large-scale automated applications of PSI-BLAST.

Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia.

OBJECTIVES: The goal of this study was to investigate the nature of the association between silent ischemia and postoperative myocardial infarction (PMI). BACKGROUND: Silent ischemia predicts cardiac morbidity and mortality in both ambulatory and postoperative patients. Whether silent stress-induced ischemia is merely a marker of extensive coronary artery disease or has a closer association with infarction has not been determined. METHODS: In 185 consecutive patients undergoing vascular surgery, we correlated ischemia duration, as detected on a continuous 12-lead ST-trend monitoring during the period 48 h to 72 h after surgery, with cardiac troponin-I (cTn-I) measured in the first three postoperative days and with postoperative cardiac outcome. Postoperative myocardial infarction was defined as cTn-I >3.1 ng/ml accompanied by either typical symptoms or new ischemic electrocardiogram (ECG) findings. RESULTS: During 11,132 patient-hours of monitoring, 38 patients (20.5%) had 66 transient ischemic events, all but one denoted by ST-segment depression. Twelve patients (6.5%) sustained PMI; one of those patients died. All infarctions were non-Q-wave and were detected by a rise in cTn-I during or immediately after prolonged, ST depression-type ischemia. The average duration ofischemia in patients with PMI was 226+/-164 min (range: 29 to 625), compared with 38+/-26 min (p = 0.0000) in 26 patients with ischemia but not infarction. Peak cTn-I strongly correlated with the longest, as well as cumulative, ischemia duration (r = 0.83 and r = 0.78, respectively). Ischemic ECG changes were completely reversible in all but one patient who had persistent new T wave inversion. All ischemic events culminating in PMI were preceded by an increase in heart rate (delta heart rate = 32+/-15 beats/min), and most (67%) of them began at the end of surgery and emergence from anesthesia. CONCLUSIONS: Prolonged, ST depression-type ischemia progresses to MI and is strongly associated with the majority of cardiac complications after vascular surgery.

Estimating the number of protein folds and families from complete genome data.

Using the data on proteins encoded in complete genomes, combined with a rigorous theory of the sampling process, we estimate the total number of protein folds and families, as well as the number of folds and families in each genome. The total number of folds in globular, water- soluble proteins is estimated at about 1000, with structural information currently available for about one-third of the number. The sequenced genomes of unicellular organisms encode from approximately 25%, for the minimal genomes of the Mycoplasmas, to 70-80% for larger genomes, such as Escherichia coli and yeast, of the total number of folds. The number of protein families with significant sequence conservation was estimated to be between 4000 and 7000, with structures available for about 20% of these.

Genome trees constructed using five different approaches suggest new major bacterial clades.

BACKGROUND: The availability of multiple complete genome sequences from diverse taxa prompts the development of new phylogenetic approaches, which attempt to incorporate information derived from comparative analysis of complete gene sets or large subsets thereof. Such attempts are particularly relevant because of the major role of horizontal gene transfer and lineage-specific gene loss, at least in the evolution of prokaryotes. RESULTS: Five largely independent approaches were employed to construct trees for completely sequenced bacterial and archaeal genomes: i) presence-absence of genomes in clusters of orthologous genes; ii) conservation of local gene order (gene pairs) among prokaryotic genomes; iii) parameters of identity distribution for probable orthologs; iv) analysis of concatenated alignments of ribosomal proteins; v) comparison of trees constructed for multiple protein families. All constructed trees support the separation of the two primary prokaryotic domains, bacteria and archaea, as well as some terminal bifurcations within the bacterial and archaeal domains. Beyond these obvious groupings, the trees made with different methods appeared to differ substantially in terms of the relative contributions of phylogenetic relationships and similarities in gene repertoires caused by similar life styles and horizontal gene transfer to the tree topology. The trees based on presence-absence of genomes in orthologous clusters and the trees based on conserved gene pairs appear to be strongly affected by gene loss and horizontal gene transfer. The trees based on identity distributions for orthologs and particularly the tree made of concatenated ribosomal protein sequences seemed to carry a stronger phylogenetic signal. The latter tree supported three potential high-level bacterial clades,: i) Chlamydia-Spirochetes, ii) Thermotogales-Aquificales (bacterial hyperthermophiles), and ii) Actinomycetes-Deinococcales-Cyanobacteria. The latter group also appeared to join the low-GC Gram-positive bacteria at a deeper tree node. These new groupings of bacteria were supported by the analysis of alternative topologies in the concatenated ribosomal protein tree using the Kishino-Hasegawa test and by a census of the topologies of 132 individual groups of orthologous proteins. Additionally, the results of this analysis put into question the sister-group relationship between the two major archaeal groups, Euryarchaeota and Crenarchaeota, and suggest instead that Euryarchaeota might be a paraphyletic group with respect to Crenarchaeota. CONCLUSIONS: We conclude that, the extensive horizontal gene flow and lineage-specific gene loss notwithstanding, extension of phylogenetic analysis to the genome scale has the potential of uncovering deep evolutionary relationships between prokaryotic lineages.

A new superfamily of putative NTP-binding domains encoded by genomes of small DNA and RNA viruses.

Statistically significant similarity was revealed between amino acid sequences of NTP-binding pattern-containing domains which are among the most conserved protein segments in dissimilar groups of ss and dsDNA viruses (papova-, parvo-, geminiviruses and P4 bacteriophage), and RNA viruses (picorna-, como- and nepoviruses) with small genomes. Within the aligned domains of 100-120 amino acid residues, three highly conserved sequence segments have been identified, i.e. 'A' and 'B' motifs of the NTP-binding pattern, and a third, C-terminal motif 'C', not described previously. The sequence of the 'B' motif in the proteins of the new superfamily is unusually variable, with substitutions, in some of the members, of the Asp residue conserved in other NTP-binding proteins. The 'C' motif is characterized by an invariant Asn residue preceded by a stretch of hydrophobic residues. As the new superfamily included a well studied DNA and RNA helicase, T antigen of SV40, helicase function could be tentatively assigned also to the other related viral putative NTP-binding proteins. On the other hand, the possibility of different and/or multiple functions for some of these proteins is discussed.

Site-directed mutagenesis of the tick-borne encephalitis virus NS3 gene reveals the putative serine protease domain of the NS3 protein.

Several mutations were introduced into the putative serine protease domain of the tick-borne encephalitis virus NS3 protein and into a possible internal cleavage site within the protein. The influence of these mutations on proteolytic activity of NS3 protein and NS3' protein formation was tested in vitro. It was found that NS3' formation was not dependent on the activity of the NS3 N-terminal serine protease. Mutations affecting the Ser-138 residue of the NS3 protein prohibited cleavage between NS2B and NS3 proteins when the NS2B-NS3 part of the viral genome was expressed in vitro, suggesting the key role of Ser-138 in viral serine protease functioning.

Winnowing sequences from a database search.

In database searches for sequence similarity, matches to a distinct sequence region (e.g., protein domain) are frequently obscured by numerous matches to another region of the same sequence. In order to cope with this problem, algorithms are developed to discard redundant matches. One model for this problem begins with a list of intervals, each with an associated score; each interval gives the range of positions in the query sequence that align to a database sequence, and the score is that of the alignment. If interval I is contained in interval J, and I's score is less than J's, then I is said to be dominated by J. The problem is then to identify each interval that is dominated by at least K other intervals, where K is a given level of "tolerable redundancy." An algorithm is developed to solve the problem in O(N log N) time and O(N*) space, where N is the number of intervals and N* is a precisely defined value that never exceeds N and is frequently much smaller. This criterion for discarding database hits has been implemented in the Blast program, as illustrated herein with examples. Several variations and extensions of this approach are also described.

Short repeats and IS elements in the extremely radiation-resistant bacterium Deinococcus radiodurans and comparison to other bacterial species.

Computer analysis of the complete genome of Deinococcus radiodurans R1 has shown that the number of insertion sequences (ISs) and small noncoding repeats (SNRs) it contains is very high, and comparable with those of Escherichia coli. IS elements and several families of SNRs are described, together with their possible function in the D. radiodurans genome.

Perceptual and memorial constructs in children's judgments of quantity: a law of across-representation invariance.

Children at three different ages made judgments of physically presented (perceptual estimation) or symbolically represented (memorial estimation) rectangles. Height and width were integrated according to different, age-dependent algebraic rules. Memorial data obeyed the same integration rules that operated in the original perceptual judgments even when younger children and older children used completely different combination models. Valuation operations were the same in perception and memory for the youngest group (6-year-olds) but became discriminably different at older ages (for the 8- and 10-year olds). Three additional experiments on judgments of volume, liquid quantity, and visual length yielded strong cross-validation support for the general invariance claim (with respect to integration rule theory) but less strong support for the specific invariance claim (with respect to valuation function for the 6-year-old subjects). Results are interpreted as demonstrating lawful and long-enduring ecological constraints on internal representation.

Integration of stimulus dimensions in perception and memory: composition rules and psychophysical relations.

A series of five experiments used the method of magnitude estimation to assess how height and width are integrated in perceptual and in memorial judgments of area. Separate groups of subjects estimated the areas of perceived or remembered rectangles produced by a symmetrical 4 X 4 factorial design of height and width. Additional independent groups of observers made area judgments, based on special mixes of perceptual and memorial information referring to the height and width components of the to-be-judged rectangles. Both perceptual and memory data obeyed the bilinear interaction prediction of the normative multiplicative model. The relation between perceived and actual area as well as the relation between remembered and actual area could both be described by a compressive power function, with the exponent being reliably smaller for remembered than for perceived area. These results seem to imply a principle of integration rule invariance across perceptual and memorial estimates of a given set of stimuli, in conjunction with characteristically different valuation operations.

Comparison of transmyometrial and transcervical embryo transfer in patients with previously failed in vitro fertilization-embryo transfer cycles and/or cervical stenosis.

OBJECTIVE: To compare ultrasound-guided transmyometrial and transcervical ET in patients with cervical stenosis or in patients who failed to conceive after at least three previous IVF-ET cycles. DESIGN: A prospective, randomized study. SETTING: The IVF-ET Unit at Serlin Maternity Hospital. PATIENT(S): Forty patients undergoing IVF-ET. INTERVENTION(S): Ultrasound-guided transvaginal, transmyometrial, versus transcervical ET. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Transmyometrial ET was performed in 20 patients and resulted in one clinical pregnancy. Transcervical ET, performed in another 20 similar patients, resulted in three clinical pregnancies. CONCLUSION(S): No benefit was derived by electing transmyometrial ET in preference to transcervical ET in patients who had failed to conceive in previous cycles.

Cervical dilatation during ovum pick-up in patients with cervical stenosis: effect on pregnancy outcome in an in vitro fertilization-embryo transfer program.

OBJECTIVE: To evaluate the results of cervical dilatation during an ovum pick-up session in patients with cervical stenosis who participated in an IVF-ET program. DESIGN: A retrospective study. SETTING: In vitro fertilization-ET unit. PATIENT(S): Forty-one treatment cycles in 22 patients with known cervical stenosis. In all patients previous transcervical ET had been either extremely difficult or impossible. INTERVENTION(S): Cervical dilatation under general anesthesia during an ovum pick-up session, 48 hours before transcervical ET. MAIN OUTCOME MEASURE(S): Ease of ET procedure and clinical pregnancy rate (PR). RESULT(S): Cervical dilatation was performed in 41 IVF-ET cycles and resulted in easier transcervical ET in 39 cycles, but only one clinical and one extrauterine pregnancy. CONCLUSION(S): Cervical dilatation during the ovum pick-up session leads to easier ET in patients with cervical stenosis, but PRs after this procedure are very low.

The effect of oophorectomy and estrogen replacement therapy on Doppler derived parameters of aortic flow.

OBJECTIVES: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. METHODS: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery - the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. RESULTS: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. CONCLUSIONS: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation.