julilili42/papers huggingface dataset:
Validation and detection of vessel landmarks by using anatomical knowledge
2010-03-04

The detection of anatomical landmarks is an important prerequisite to analyze medical images fully automatically. Several machine learning approaches have been proposed to parse 3D CT datasets and to determine the location of landmarks with associated uncertainty. However, it is a challenging task to incorporate high-level anatomical knowledge to improve these classification results. We propose a new approach to validate candidates for vessel bifurcation landmarks which is also applied to systematically search missed and to validate ambiguous landmarks. A knowledge base is trained providing human-readable geometric information of the vascular system, mainly vessel lengths, radii and curvature information, for validation of landmarks and to guide the search process. To analyze the bifurcation area surrounding a vessel landmark of interest, a new approach is proposed which is based on Fast Marching and incorporates anatomical information from the knowledge base. Using the proposed algorithms, an anatomical knowledge base has been generated based on 90 manually annotated CT images containing different parts of the body. To evaluate the landmark validation a set of 50 carotid datasets has been tested in combination with a state of the art landmark detector with excellent results. Beside the carotid bifurcation the algorithm is designed to handle a wide range of vascular landmarks, e.g. celiac, superior mesenteric, renal, aortic, iliac and femoral bifurcation.
Evaluation of Geiger-mode APDs for PET block detector designs
2010-03-05

This paper presents an evaluation of two types of Geiger-mode avalanche photodiodes (G-APDs) for their potential to be used in a positron emission tomography (PET) detector. While the MPPC G-APD had only 3600 cells, the solid state photomultiplier (SSPM)-type G-APD had 8100 cells. In a single-channel G-APD/LSO setup, the energy resolution (DeltaEpsilon/Epsilon) of the SSPM at 511 keV was 25%, while the (DeltaEpsilon/Epsilon) of the MPPC was 13.5% (FWHM). No influences were observed while the detectors were inside a 7 T magnetic resonance (MR) scanner. A time resolution of 2.7 ns (FWHM) was measured for the LSO/SSPM and 0.9 ns for the LSO/MPPC detector setup. Although the linearity was superior for the SSPM in the single detector readout, the inferior energy and time resolution excluded them to be used for the block detector readout. All 12 x 12 LSO crystals of the block could be resolved in a crystal map using a 3 x 3 MPPC G-APD array. The time resolution of the block detector was 950 ps. While the energy spectra for the MPPC-based single-channel setup were nonlinear, they reached linearity better than 5% in the block detector. A high number of G-APD cells provide a linear signal in a single-channel detector setup, but not necessarily a good timing or (DeltaEpsilon/Epsilon) due to a larger inactive surface resulting in lower photon detection efficiency. G-APDs with a low number of cells provide a good timing and (DeltaEpsilon/Epsilon) and linear signals in block detector designs, where the scintillation light is shared over many G-APDs.
Influence of 5‐aminosalicylic acid on 6‐thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy
2010-03-05

Background and purpose: 5‐aminosalicylate (5‐ASA) raises levels of 6‐thioguanine nucleotides (6‐TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN – 6‐thioguanosine mono‐, di‐ and triphosphate (6‐TGMP, 6‐TGDP, 6‐TGTP) – and of 6‐methylmercaptopurine ribonucleotides (6‐MMPR) after 5‐ASA are not known. Experimental approach: Effects of increasing 5‐ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4‐week study periods. Patients started with 2 g 5‐ASA daily, and then were increased to 4 g daily and followed by a washout period. Thiopurine doses remained unchanged throughout the entire study. Levels of 6‐TGMP, 6‐TGDP, 6‐TGTP and 6‐MMPR as well as of 5‐ASA and N‐acetyl‐5‐aminosalicylic acid (N‐Ac‐5‐ASA) were determined each study period. Key results: Median baseline levels in 17 patients of 6‐TGDP, 6‐TGTP and 6‐MMPR were 52, 319 and 1676 pmol per 8 × 10 8 red blood cells respectively. After co‐administration of 2 g 5‐ASA daily, median 6‐TGDP and 6‐TGTP levels increased but median 6‐MMPR levels were unchanged. Increasing 5‐ASA to 4 g daily did not affect median 6‐TGDP and 6‐TGTP levels, but median 6‐MMPR levels decreased. After discontinuation of 5‐ASA, both 6‐TGDP and 6‐TGTP levels decreased and median 6‐MMPR levels increased. The 6‐TGTP/(6‐TGDP+6‐TGTP)‐ratio did not change during the study, but 6‐MMPR/6‐TGN ratios decreased. Conclusions and implications: Individual 6‐TGN metabolites increased after addition of 5‐ASA, but 6‐MMPR‐levels and the 6‐MMPR/6‐TGN ratios decreased. Further studies are needed to decide whether this pharmacokinetic interaction would result in improvement of efficacy and/or increased risk of toxicity of AZA.
Magmatic Evolution of Anorthosites of the Kunene Intrusive Complex, NW Namibia: Evidence from Oxygen Isotope Data and Trace Element Zoning
2010-03-05

In the Mesoproterozoic Kunene Intrusive Complex (Angola–Namibia) one of the largest massif-type anorthosite complexes in the world, two successively emplaced anorthosite varieties can be recognized. The older white anorthosite suite consists of pyroxene-bearing anorthosite and leucogabbronorite, whereas the younger dark anorthosite suite is dominated by olivine-bearing anorthosite and leucotroctolite. The oxygen isotope and trace element characteristics of plagioclase and minor phases of the two distinct anorthosite varieties are consistent with their derivation from a mantle-derived parental melt that was subject to crustal contamination during the early stages of evolution. The trace element zoning patterns of plagioclase demonstrate that the older white anorthosite was derived by simultaneous fractional crystallization of plagioclase, pyroxene and Fe–Ti oxides during and after crustal contamination. In contrast, the subsequently emplaced dark anorthosite evolved after replenishment with mantle-derived parental melts by fractional crystallization of plagioclase, olivine and Fe–Ti oxides at magmatic temperatures above 1150°C and experienced less crustal contamination.
SP1-Dependent Induction of CD39 Facilitates Hepatic Ischemic Preconditioning
2010-03-06

Abstract Ischemia/reperfusion injury (IRI) of the liver is an important cause of hepatic dysfunction. Ischemic preconditioning (IP) is associated with adenosine-mediated tissue protection from subsequent IRI. Extracellular nucleotides (e.g., ATP) represent the main source for extracellular adenosine. Therefore, we hypothesized that phosphohydrolysis of ATP/ADP via the ectonucleoside triphosphate diphosphohydrolase-1 (CD39), conversion of ATP/ADP to AMP, mediates IP-dependent liver protection. We found that hepatic IP was associated with significant induction of CD39 transcript, heightened protein expression, and improved outcomes after IRI. Targeted gene deletion or pharmacological inhibition of CD39 abolished hepatoprotection by IP as measured by serum markers of liver injury or histology. Therapeutic studies to mimic IP with i.p. apyrase (a soluble ectonucleoside triphosphate diphosphohydrolase, NTPDase) in the absence of IP attenuated hepatic injury after IRI. In additional in vivo studies, small interfering RNA treatment was used to achieve repression of the transcription factor Sp1, known to be implicated in CD39 transcriptional regulation. In fact, Sp1 small interfering RNA treatment was associated with attenuated CD39 induction and increased hepatic injury in vivo. Our data suggest a Sp1-dependent regulatory pathway for CD39 during hepatic IP. These studies reveal a novel role of CD39 in hepatic protection and suggest soluble apyrase for the treatment of liver ischemia.
Advantage of Upregulation of Succinate Dehydrogenase in Staphylococcus aureus Biofilms
2010-03-06

ABSTRACT Previous studies have demonstrated that various tricarboxylic acid (TCA) cycle genes, particularly the succinate dehydrogenase genes ( sdhCAB ), are upregulated in Staphylococcus aureus biofilms. To better study the role of this enzyme complex, an sdhCAB deletion mutant (Δ sdh ) was constructed. Compared to the wild type (wt) the mutant was impaired in planktonic growth under aerobic conditions, excreted acetic acid could not be reused and accumulated continuously, succinate was excreted and found in the culture supernatant, and metabolome analysis with cells grown in chemically defined medium revealed reduced uptake/metabolism of some amino acids from the growth medium. Moreover, the mutant was able to counteract the steadily decreasing extracellular pH by increased urease activity. The addition of fumarate to the growth medium restored the wt phenotype. The mutant showed a small-colony variant (SCV)-like phenotype, a slight increase in resistance to various aminoglycoside antibiotics, and decreased pigmentation. The decreased growth under aerobic conditions is due to the interruption of the TCA cycle (indicated by the accumulation of succinate and acetic acid) with the consequence that many fewer reduction equivalents (NADH and FADH 2 ) can fuel the respiratory chain. The results indicate that the TCA cycle is required for acetate and amino acid catabolism; its upregulation under biofilm conditions is advantageous under such nutrient- and oxygen-limited conditions.
Plant survival in relation to seed size along environmental gradients: a long‐term study from semi‐arid and Mediterranean annual plant communities
2010-03-08

Summary 1. A positive relationship between seed size and subsequent offspring survival is a key assumption in ecological theory concerning life‐history strategies. Yet, this relationship is uncertain in respect to lifetime survival because sound evidence only exists for early seedling stages. Furthermore, the effect of environmental variation in space and time, and of contrasting plant functional groups, on this relationship has been scarcely examined. 2. Here, we investigated survival and between‐year variation therein. We tested for both whether their relationship to seed size (i) is maintained up until reproduction, (ii) changes along environmental gradients and (iii) differs between functional groups (grasses, legumes, forbs). 3. Survival was monitored from established seedlings to reproductive plants in 49 annual species under natural conditions during 7 years in three sites along a steep rainfall gradient. We then related average survival per species and between‐year variation in survival to seed size, site along the gradient and functional group. 4. Larger seed size was associated with higher survival and lower between‐year variation. Across the rainfall gradient, we detected no difference in the seed size–survival relationships; however, variation between years was lowest in the most mesic site where no relationship for between‐year variation with seed size was observed. Legumes showed lower survival and higher between‐year variation than grasses. 5. Our findings indicate that larger seed size provides survival advantages beyond seedling establishment up until reproduction among annual species. Larger seed size also provides a bet‐hedging strategy in temporally unpredictable environments. Increased abiotic favourability along environmental gradients may have little effect on survival rates but reduces survival variation between years and thus reduces the bet‐hedging benefit of larger seed size. We suggest that the contrasting response of legumes and grasses may partly result from their disparity in seed dormancy. 6. Synthesis . Current plant life‐history theory can be refined by accounting for both benefits of larger seed size, higher survival rates and bet‐hedging. Studies along environmental gradients are needed to generalize findings across ecosystems and to predict patterns of plant traits and plant performance under changing environmental conditions.
Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes
2010-03-08

It has been suggested that cGMP kinase I (cGKI) dampens cardiac hypertrophy. We have compared the effect of isoproterenol (ISO) and transverse aortic constriction (TAC) on hypertrophy in WT [control (CTR)] mice, total cGKI-KO mice, and cGKIβ rescue mice (βRM) lacking cGKI specifically in cardiomyocytes (CMs). Infusion of ISO did not change the expression of cGKI in the hearts of CTR mice or βRM but raised the heart weight by ∼20% in both. An identical hypertrophic growth response was measured in CMs from CTR mice and βRM and in isolated adult CMs cultured with or without 1 μM ISO. In both genotypes, ISO infusion induced similar changes in the expression of hypertrophy-associated cardiac genes and significant elevation of serum atrial natriuretic peptide and total cardiac cGMP. No differences in cardiac hypertrophy were obtained by 7-day ISO infusion in 4- to 6-week-old conventional cGKI-KO and CTR mice. Furthermore, TAC-induced hypertrophy of CTR mice and βRM was not different and did not result in changes of the cGMP-hydrolyzing phosphodiesterase activities in hypertropic hearts or CMs. These results strongly suggest that cardiac myocyte cGKI does not affect the development of heart hypertrophy induced by pressure overload or chronic ISO infusion.
Design of an automotive traffic sign recognition system targeting a multi-core SoC implementation
2010-03-08

This paper describes the design of an automotive traffic sign recognition application. All stages of the design process, starting on system-level with an abstract, pure functional model down to final hardware/software implementations on an FPGA, are shown. The proposed design flow tackles existing bottlenecks of today's system-level design processes, following an early model-based performance evaluation and analysis strategy, which takes into account hardware, software and real-time operating system aspects. The experiments with the traffic sign recognition application show, that the developed mechanisms are able to identify appropriate system configurations and to provide a seamless link into the underlying implementation flows.
Towards assertion-based verification of heterogeneous system designs
2010-03-08

In this paper a comprehensive assertion-based verification methodology for the digital, analog and software domain of heterogeneous systems is presented. The proposed methodology combines a novel mixed-signal assertion language and the corresponding automatic verification algorithm. The algorithm translates the heterogeneous temporal properties into observer automata for a semi-formal verification. This enables automatic verification of complex heterogeneous properties that can not be verified by existing approaches. The experimental results show the integration of mixed-signal assertions into a simulation environment and demonstrate the broad applicability and the high value of the evolved solution.
The use of endoscopy in fetal medicine
2010-03-08

We aimed to review the state of affairs in the field of embryo–fetoscopy as well as its instrumental requirements. Today, endoscopic procedures of limited complexity are easily possible within the amniotic cavity. Embryoscopy is typically done for diagnostic purposes, such as the demonstration of external anomalies very early in pregnancy and/or obtaining embryonic tissues in recurrent miscarriages. Fetoscopy is the direct visualization of the amniotic cavity from the second trimester onwards. Its principal indications are complications of monochorionic twinning and severe congenital diaphragmatic hernia. There is level I evidence that fetoscopic laser surgery for twin–twin-transfusion syndrome is superior over amniodrainage. Fetoscopic endoluminal tracheal occlusion is done for severe diaphragmatic hernia. Whether tracheal occlusion yields better outcomes than expectant management during pregnancies is currently being investigated in a randomized trial. There are a number of less common procedures discussed as well. Overall, maternal risks of embryo–fetoscopy are minimal. The most frequent complication is rupture of the membranes and as a consequence preterm delivery. Fetal surgery seems safe and has, therefore, become a clinical reality. Although the stage of technical experimentation is over, most interventions remain investigational. Inclusion of patients into trials whenever possible should be encouraged, rather than building up casuistic experience.
Repair of Global Regulators inStaphylococcus aureus8325 and Comparative Analysis with Other Clinical Isolates
2010-03-09

ABSTRACT The pathogenicity of Staphylococcus aureus strains varies tremendously (as seen with animals). It is largely dependent on global regulators, which control the production of toxins, virulence, and fitness factors. Despite the vast knowledge of staphylococcal molecular genetics, there is still widespread dispute over what factors must come together to make a strain highly virulent. S. aureus NCTC8325 (RN1 and derivatives) is a widely used model strain for which an incomparable wealth of knowledge has accumulated in the almost 50 years since its isolation. Although RN1 has functional agr , sarA , and sae global regulators, it is defective in two regulatory genes, rsbU (a positive activator of SigB) and tcaR (an activator of protein A transcription), and is therefore considered by many to be a poor model for studies of regulation and virulence. Here, we repaired these genes and compared the resulting RN1 derivatives with other widely used strains, Newman, USA300, UAMS-1, and COL, plus the parental RN1, with respect to growth, extracellular protein pattern, hemolytic activity, protein A production, pigmentation, biofilm formation, and mouse lethality. The tcaR -repaired strain, showed little alteration in these properties. However, the rsbU -repaired strain was profoundly altered. Hemolytic activity was largely decreased, the exoprotein pattern became much more similar to that of typical wild-type (wt) S. aureus , and there was a surprising increase in mouse lethality. We note that each of the strains tested has a mutational alteration in one or more other regulatory functions, and we conclude that the repaired RN1 is a good model strain for studies of staphylococcal regulation and pathobiology; although strain Newman has been used extensively for such studies in recent years, it has a missense mutation in saeS , the histidine kinase component of the sae signaling module, which profoundly alters its regulatory phenotype. If this mutation were repaired, Newman would be considerably improved as a model strain.
Role of the (p)ppGpp Synthase RSH, a RelA/SpoT Homolog, in Stringent Response and Virulence ofStaphylococcus aureus
2010-03-09

ABSTRACT In most bacteria, nutrient limitations provoke the stringent control through the rapid synthesis of the alarmones pppGpp and ppGpp. Little is known about the stringent control in the human pathogen Staphylococcus aureus , partly due to the essentiality of the major (p)ppGpp synthase/hydrolase enzyme RSH (RelA/SpoT homolog). Here, we show that mutants defective only in the synthase domain of RSH ( rsh syn ) are not impaired in growth under nutrient-rich conditions. However, these mutants were more sensitive toward mupirocin and were impaired in survival when essential amino acids were depleted from the medium. RSH is the major enzyme responsible for (p)ppGpp synthesis in response to amino acid deprivation (lack of Leu/Val) or mupirocin treatment. Transcriptional analysis showed that the RSH-dependent stringent control in S. aureus is characterized by repression of genes whose products are predicted to be involved in the translation machinery and by upregulation of genes coding for enzymes involved in amino acid metabolism and transport which are controlled by the repressor CodY. Amino acid starvation also provoked stabilization of the RNAs coding for major virulence regulators, such as SaeRS and SarA, independently of RSH. In an animal model, the rsh syn mutant was shown to be less virulent than the wild type. Virulence could be restored by the introduction of a codY mutation into the rsh syn mutant. These results indicate that stringent conditions are present during infection and that RSH-dependent derepression of CodY-regulated genes is essential for virulence in S. aureus .
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias
2010-03-09

Objectives: These EFNS guidelines on the molecular diagnosis of channelopathies, including epilepsy and migraine, as well as stroke, and dementia are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work‐up is indicated. Search strategy: To collect data about planning, conditions, and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta‐analyses, review papers, and guideline recommendations were reviewed. Results: The best level of evidence for genetic testing recommendation (B) can be found for a small number of syndromes, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, severe myoclonic epilepsy of infancy, familial recurrent hemorrhages, familial Alzheimer’s disease, and frontotemporal lobar degeneration. Good practice points can be formulated for a number of other disorders. Conclusion: These guidelines are provisional, and the future availability of molecular genetic epidemiological data about the neurogenetic disorders under discussion in our article will allow improved recommendation with an increased level of evidence.
Total Synthesis and Configurational Assignment of Chondramide A
2010-03-10

Abstract The first total synthesis of the cyclodepsipeptide chondramide A ( 2 b ) is described. This depsipeptide is composed of four subunits, namely L ‐alanine, N ‐Me‐ D ‐tryptophan, 3‐amino‐2‐methoxy‐propionic acid (β‐tyrosine derivative), and a 7‐hydroxy‐alkenoic acid. While the configuration of the stereogenic centers in the 7‐hydroxy‐alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2 S ,3 R ) or (2 L ,3 L ), respectively. The synthesis of the 3‐amino‐2‐methoxy‐3‐arylpropanoic ester 20 b relied on an asymmetric dihydroxylation yielding diol ent ‐ 15 a followed by a regioselective Mitsunobu substitution leading to 3‐azido‐2‐hydroxypropanoate 18 b . We could also show that the ester bond in the seco compound 26 b can be fashioned by a Mitsunobu esterification by using hydroxy ester (7 S )‐ 7 and the tripeptide acid 25 b . This synthesis should allow for the preparation of various analogues.