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Wine is composed of multitudinous flavour components and volatile organic compounds that provide this beverage with its attractive properties of taste and aroma. The perceived quality of a wine can be attributed to the absolute and relative concentrations of favourable aroma compounds; hence, increasing the detectable levels of an attractive aroma, such as β-ionone with its violet and berry notes, can improve the organoleptic qualities of given wine styles. We here describe the generation of a new grape-must fermenting strain of Saccharomyces cerevisiae that is capable of releasing β-ionone through the heterologous expression of both the enzyme carotenoid cleavage dioxygenase 1 (CCD1) and its substrate, β-carotene. Haploid laboratory strains of S. cerevisiae were constructed with and without integrated carotenogenic genes and transformed with a plasmid containing the genes of CCD1. These strains were then mated with a sporulated diploid wine industry yeast, VIN13, and four resultant crosses—designated MQ01–MQ04–which were capable of fermenting the must to dryness were compared for their ability to release β-ionone. Analyses of their fermentation products showed that the MQ01 strain produced a high level of β-ionone and offers a fermenting hybrid yeast with the potential to enhance the organoleptic qualities of wine.

This study investigated the ability of a navigation filter to process multiple terrain-based sensors, such as slant-range, slant-speed, and terrain relative navigation sensors, during a descent-to-...

Acute Respiratory Distress Syndrome (ARDS), also known as noncardiogenic pulmonary edema, is a severe condition that affects around one in ten-thousand people every year with life-threatening consequences. Its pathophysiology is characterized by bronchoalveolar injury and alveolar collapse (i.e., atelectasis), whereby its patient diagnosis is based on the so-called ‘Berlin Definition‘. One common practice in Intensive Care Units (ICUs) is to use lung recruitment manoeuvres (RMs) in ARDS to open up unstable, collapsed alveoli using a temporary increase in transpulmonary pressure. Many RMs have been proposed, but there is also confusion regarding the optimal way to achieve and maintain alveolar recruitment in ARDS. Therefore, the best solution to prevent lung damages by ARDS is to identify the onset of ARDS which is still a matter of research. Determining ARDS disease onset, progression, diagnosis, and treatment required algorithmic support which in turn raises the demand for cutting-edge computing power. This paper thus describes several different data science approaches to better understand ARDS, such as using time series analysis and image recognition with deep learning methods and mechanistic modelling using a lung simulator. In addition, we outline how High-Performance Computing (HPC) helps in both cases. That also includes porting the mechanistic models from serial MatLab approaches and its modular supercomputer designs. Finally, without losing sight of discussing the datasets, their features, and their relevance, we also include broader selected lessons learned in the context of ARDS out of our Smart Medical Information Technology for Healthcare (SMITH) research project. The SMITH consortium brings together technologists and medical doctors of nine hospitals, whereby the ARDS research is performed by our Algorithmic Surveillance of ICU (ASIC) patients team. The paper thus also describes how it is essential that HPC experts team up with medical doctors that usually lack the technical and data science experience and contribute to the fact that a wealth of data exists, but ARDS analysis is still slowly progressing. We complement the ARDS findings with selected insights from our Covid-19 research under the umbrella of the European Open Science Cloud (EOSC) fast track grant, a very similar application field.

Traditionally, the use of malolactic fermentation gives rise to microbiologically stable wines. However, malolactic fermentation is not free from possible collateral effects that can take place under specific scenarios. The present work tests the influence of different biological deacidification strategies on the volatile and non-volatile components of white must from Germany. The study compared mixed cultures of Lachancea thermotolerans and Schizosaccharomyces pombe and a pure culture of Sc. pombe to the classical biological deacidification process performed by lactic acid bacteria. Strains of Oenococcus oeni and Lactiplantibacillus plantarum were co- or sequentially inoculated with S. cerevisiae to carry out malolactic fermentation. Different fermentation treatments took place at a laboratory scale of 0.6 L in vessels of 0.75 L. The instrumental techniques Fourier-transform mid-infrared spectroscopy (FT-MIR), high performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS) were used to evaluate different chemical parameters in the final wines. The results showed the ability of Sc. pombe to consume malic acid in combination with L. thermotolerans without using S. cerevisiae or lactic acid bacteria. Fermentations involving Sc. pombe consumed all the malic acid, although they reduced the concentrations of higher alcohols, fatty acids and acetic acid. Simultaneous alcoholic and malolactic fermentations reduced malic acid by about 80%, while classical malolactic fermentation reduced it by 100%. Fermentations involving L. thermotolerans produced the highest lactic acid, ester and glycerol concentrations.

Vein mineralization observed in boreholes, quarries and outcrops of Upper Permian and Mesozoic sediments in the Thuringian Syncline, Germany, was investigated for the first time by petrography, electron microprobe analysis and stable isotope analysis. The objective was a characterization of paleo-fluid systems within this basin. Veins are mostly restricted to NW-SE trending fault systems and comprise carbonates (calcite, dolomite), minor sulfates (gypsum/anhydrite, celestite, barite), and rarely sulfides. They are variably distributed within the Late Paleozoic to Mesozoic succession. Calcite vein mineralization occurs in almost all Triassic strata, though dominating in the Lower Muschelkalk subgroup (mu). Gypsum/anhydrite veins occur in the Middle Keuper subgroup (km), Middle Muschelkalk subgroup (mm), Middle and Upper Buntsandstein subgroup (sm, so) as well as in the Upper Permian (Zechstein). Sulfate and carbonate isotope analyses indicate that most vein mineralization dominantly crystallized from intraformational fluids within the Upper Permian and Triassic sediments. Crystallization from descending meteoric waters was observed especially for calcite veins in the Lower Muschelkalk, but also for gypsum/anhydrite veins in the Upper Buntsandstein. Mineralization from ascending, carbonate-pH-buffered, warm waters was restricted to individual parts of the southern, deep reaching main border fault zone of the Thuringian Syncline. Mixing and fault crossing fluid movements are subordinate within the Thuringian Syncline. We conclude that no large scale cross-formational fluid flow occurred in Thuringian Syncline over the last millions of years.

An increasing number of data science approaches that take advantage of deep learning in computational medicine and biomedical engineering require parallel and scalable algorithms using High-Performance Computing systems. Especially computational methods for analysing clinical datasets that consist of multivariate time series data can benefit from High-Performance Computing when applying computing-intensive Recurrent Neural Networks. This paper proposes a dynamic data science platform consisting of modular High-Performance Computing systems using accelerators for innovative Deep Learning algorithms to speed-up medical applications that take advantage of large biomedical scientific databases. This platform's core idea is to train a set of Deep Learning models very fast to easily combine and compare the different Deep Learning models' forecast (out-of-sample) performance to their past (in-sample) performance. Considering that this enables a better understanding of what Deep Learning models can be useful to apply to specific medical datasets, our case study leverages the three data science methods Gated Recurrent Units, one-dimensional convolutional layers, and their combination. We validate our approach using the open MIMIC-III database in a case study that assists in understanding, diagnosing, and treating a specific condition that affects Intensive Care Unit patients, namely Acute Respiratory Distress Syndrome.

In eukaryotic cells, the production of cellular energy requires close interplay between nuclear and mitochondrial genomes. The mitochondrial genome is essential in that it encodes several genes involved in oxidative phosphorylation. Each cell contains several mitochondrial genome copies and mitochondrial DNA recombination is a widespread process occurring in plants, fungi, protists, and invertebrates. Saccharomyces cerevisiae has proved to be an excellent model to dissect mitochondrial biology. Several studies have focused on DNA recombination in this organelle, yet mostly relied on reporter genes or artificial systems. However, no complete mitochondrial recombination map has been released for any eukaryote so far. In the present work, we sequenced pools of diploids originating from a cross between two different S. cerevisiae strains to detect recombination events. This strategy allowed us to generate the first genome-wide map of recombination for yeast mitochondrial DNA. We demonstrated that recombination events are enriched in specific hotspots preferentially localized in non-protein-coding regions. Additionally, comparison of the recombination profiles of two different crosses showed that the genetic background affects hotspot localization and recombination rates. Finally, to gain insights into the mechanisms involved in mitochondrial recombination, we assessed the impact of individual depletion of four genes previously associated with this process. Deletion of NTG1 and MGT1 did not substantially influence the recombination landscape, alluding to the potential presence of additional regulatory factors. Our findings also revealed the loss of large mitochondrial DNA regions in the absence of MHR1, suggesting a pivotal role for Mhr1 in mitochondrial genome maintenance during mating. This study provides a comprehensive overview of mitochondrial DNA recombination in yeast and thus paves the way for future mechanistic studies of mitochondrial recombination and genome maintenance.

Internet est devenu un outil incontournable d’information dans le domaine de la sante. On estime qu’environ trois quart des patients y effectue des recherches. De plus, les patients obeses semblent particulierement interesses par cet outil. Cette etude analyse la qualite des sites web francais les plus populaires en chirurgie bariatrique. Entre septembre et octobre 2013, nous avons selectionne 20 sites web sur le theme de la chirurgie bariatrique. La recherche a ete realisee avec le moteur de recherche Google® en utilisant quatre mots cles : « chirurgie obesite », « by-pass gastrique », « anneau gastrique », et « sleeve ». Les sites ont ete evalues grâce a un outil d’analyse des sites web recommande par l’HAS, et classes en 3 categories : « tres bien », « bien » et « faible ». Nous avons aussi retenu pour chaque site l’organisme d’affiliation et la labellisation HON (Health On the Net). La Societe Francaise et Francophone de Chirurgie de l’Obesite et des Maladies Metaboliques (SOFFCO-MM) a ete inclus d’office. Environ la moitie des sites web retenus (9/20) emanent d’etablissements de sante prives, huit sont rediges par des organismes de communication, deux sites sont institutionnels et un seul appartient a un hopital public. Sept sites (35 %) ont ete classes « tres bien », cinq (25 %) ont ete classes « bien », et huit (40 %) comme « faible ». Les sites des etablissements de sante (publiques ou prives) ont obtenu de meilleurs resultats compare aux sites rediges par des organismes de communication ou par des institutions (p

Dissecting the molecular basis of quantitative traits is a significant challenge and is essential for understanding complex diseases. Even in model organisms, precisely determining causative genes and their interactions has remained elusive, due in part to difficulty in narrowing intervals to single genes and in detecting epistasis or linked quantitative trait loci. These difficulties are exacerbated by limitations in experimental design, such as low numbers of analyzed individuals or of polymorphisms between parental genomes. We address these challenges by applying three independent high-throughput approaches for QTL mapping to map the genetic variants underlying 11 phenotypes in two genetically distant Saccharomyces cerevisiae strains, namely (1) individual analysis of >700 meiotic segregants, (2) bulk segregant analysis, and (3) reciprocal hemizygosity scanning, a new genome-wide method that we developed. We reveal differences in the performance of each approach and, by combining them, identify eight polymorphic genes that affect eight different phenotypes: colony shape, flocculation, growth on two nonfermentable carbon sources, and resistance to two drugs, salt, and high temperature. Our results demonstrate the power of individual segregant analysis to dissect QTL and address the underestimated contribution of interactions between variants. We also reveal confounding factors like mutations and aneuploidy in pooled approaches, providing valuable lessons for future designs of complex trait mapping studies.

Transposable element (TE) evolution in genomes has mostly been deduced from comparative genome analyses. TEs often account for a large proportion of the eukaryotic nuclear genome (up to 50%, depending on the species). Among the many existing genomic copies, only a small fraction may contribute to the mobility of a TE family. We have identified here, using a genetic screening procedure to trap Ty1 long terminal repeat-retrotransposon insertions in Saccharomyces cerevisiae, which among the populations of resident Ty1 copies are responsible for Ty1 mobility. Although the newly inserted Ty1 copies resulting from a single round of transposition were found to originate from a limited subset of Ty1 resident copies, they showed a high degree of diversity at the nucleotide level, mainly due to the reverse transcription-mediated recombination. In this process, highly expressed and strikingly nonautonomous mutant Ty1 were found to be the most frequently used resident copies, which suggests that nonautonomous elements play a key role in the dynamics of the Ty1 family.

Cardiac toxicity of the new anthracycline antitumour antibiotics violamycin BI (V) and carminomycin (C) was studied in comparison with daunorubicin (D). Rabbits were intravenously given total doses of 0.1-1.5 mg/kg V or C, and 0.64-18 mg/kg D, respectively, twice weekly for one month. When examined two to six days, two and four weeks, respectively, after the last drug administration the gross findings consisted of hydropericard, hydrothorax and ascites in some animals. Histologically, loss of striation and focal necrosis of cardiac muscle cells and subsequently chronic inflammatory reactions and/or proliferation of mesenchyma cells were mostly found. These alterations were somewhat more pronounced in rabbits treated with V than in animals received D or C. At equitoxic doses of the antibiotics tested the ultrastructural lesion in the myocardial cells were altogether less marked after treatment with D than with C or V.

Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level

The prevalence of Campylobacter pylori in gastric mucosa was investigated prospectively (by histology, cytology, bacterial culture and urease rapid-test) in 302 patients of a routine gastroenterological endoscopy programme. According to the histopathological findings the following prevalence of C. pylori was established: 3 of 35 normals (9%); 116 of 167 with antral gastritis (69%), 28 of 40 with gastric ulcers (70%); 26 of 33 with duodenal ulcers (79%); 5 of 27 with other conditions (19%). The activity degree of the gastritis correlated closely with the presence of C. pylori. In a prospective open trial 110 patients with antral gastritis or gastroduodenal ulcer were treated according to the following schedule: (a) bismuth subsalicylate, 1800 mg/d for four weeks (35 patients); (b) amoxycillin 2250 mg/d for two weeks (6); (c) ranitidine 300 mg/d for four weeks (26); (d) bismuth plus amoxycillin (20); (e) bismuth plus ranitidine (23). Immediately after the end of treatment and four weeks later the elimination rates were: (a) bismuth 51% (18) and 23% (8), respectively; (b) amoxycillin 50% (3) and 17% (1); (c) ranitidine 0% (0); (d) bismuth plus amoxycillin 60% (12) and 25% (5); (e) bismuth plus ranitidine 43% (10) and 17% (4). These data indicate that treatment with bismuth plus amoxycillin will achieve a negative bacterial result in about half the patients. But frequently as early as four weeks later C. pylori can again be demonstrated, so that the long-term elimination rate is only 15-30%.

Studying spontaneous chromosomal rearrangements throws light on the rules underlying the genome reshaping events occurring in eukaryotic cells, which are part of the evolutionary process. In Saccharomyces cerevisiae, translocation and deletion processes have been frequently described in haploids, but little is known so far about these processes at the diploid level. Here we investigated the nature and the frequency of the chromosomal rearrangements occurring at this ploidy level. Using a positive selection screen based on a particular mutated allele of the URA2 gene, spontaneous diploid revertants were selected and analysed. Surprisingly, the diploid state was found to be correlated with a decrease in chromosome rearrangement frequency, along with an increase in the complexity of the rearrangements occurring in the target gene. The presence of short DNA tandem repeat sequences seems to be a key requirement for deletion and reciprocal translocation processes to occur in diploids. After discussing the differences between the haploid and diploid levels, some mechanisms possibly involved in chromosome shortening and arm exchange are suggested.

We present a modified approach of chromatin immuno-precipitation followed by sequencing (ChIP-Seq), which relies on the direct ligation of molecular barcodes to chromatin fragments, thereby permitting experimental scale-up. With Bar-ChIP now enabling the concurrent profiling of multiple DNA-protein interactions, we report the simultaneous generation of 90 ChIP-Seq datasets without any robotic instrumentation. We demonstrate that application of Bar-ChIP to a panel of Saccharomyces cerevisiae chromatin-associated mutants provides a rapid and accurate genome-wide overview of their chromatin status. Additionally, we validate the utility of this technology to derive novel biological insights by identifying a role for the Rpd3S complex in maintaining H3K14 hypo-acetylation in gene bodies. We also report an association between the presence of intragenic H3K4 tri-methylation and the emergence of cryptic transcription in a Set2 mutant. Finally, we uncover a crosstalk between H3K14 acetylation and H3K4 methylation in this mutant. These results show that Bar-ChIP enables biological discovery through rapid chromatin profiling at single-nucleosome resolution for various conditions and protein modifications at once.

Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to identify pathways of interest. Here we demonstrate that modulating the sorting of nuclear-encoded proteins into mitochondria, mediated by the TIM23 complex, proves therapeutic in both yeast and patient-derived cells exhibiting ATP synthase deficiency. Targeting TIM23-dependent protein sorting improves an array of phenotypes associated with ATP synthase disorders, including biogenesis and activity of the oxidative phosphorylation machinery. Our study establishes mitochondrial protein sorting as an intervention point for ATP synthase disorders, and because of the central role of this pathway in mitochondrial biogenesis, it holds broad value for the treatment of mitochondrial diseases., Effective treatment options for mitochondrial diseases are scarce. Here, Aiyar et al. identify the TIM23 mitochondrial protein sorting machinery as a potential intervention point for mitochondrial ATP synthase disorders.

We extend a recent three-loop calculation of nuclear matter in chiral perturbation theory by including the effects from two-pion exchange with single and double virtual $\Delta(1232)$-isobar excitation. Regularization dependent short-range contributions from pion-loops are encoded in a few NN-contact coupling constants. The empirical saturation point of isospin-symmetric nuclear matter, $\bar E_0 = -16 $MeV, $\rho_0 = 0.16 $fm$^{-3}$, can be well reproduced by adjusting the strength of a two-body term linear in density (and weakening an emerging three-body term quadratic in density). The nuclear matter compressibility comes out as $K = 304 $MeV. The real single-particle potential $U(p,k_{f0})$ is substantially improved by the inclusion of the chiral $\pi N\Delta$-dynamics: it grows now monotonically with the nucleon momentum $p$. The effective nucleon mass at the Fermi surface takes on a realistic value of $M^*(k_{f0})=0.88M$. As a consequence of these features, the critical temperature of the liquid-gas phase transition gets lowered to the value $T_c \simeq 15 $MeV. In this work we continue the complex-valued single-particle potential $U(p,k_f)+i W(p,k_f)$ into the region above the Fermi surface $p>k_f$. The effects of $2\pi$-exchange with virtual $\Delta$-excitation on the nuclear energy density functional are also investigated. The effective nucleon mass associated with the kinetic energy density is $\widetilde M^*(\rho_0)= 0.64M$. Furthermore, we find that the isospin properties of nuclear matter get significantly improved by including the chiral $\pi N\Delta$-dynamics., Comment: 28 pages, 13 figures

Laparoscopic colorectal resection may induce bladder and sexual dysfunction secondary to injury to the autonomic nervous system. The aim of this study was to evaluate urinary and sexual function in male patients after laparoscopic colorectal resection for diverticular disease.From January 1997 to March 2002, we performed a retrospective analysis of urinary and sexual function in 56 consecutive male patients who had undergone laparoscopic colorectal resection for diverticular disease. Preoperative and 6-month postoperative assessment was carried out using data collected via standardized postal questionnaires.Three patients were excluded (one had a prior prostatectomy, one had Peyronie's disease, and one was treated with neuroleptics). Fifty-three patients with a mean age of 54 A+/- 2 years were included in the study. There were no conversions. The morbidity rate was 9.4%. Mean follow-up was 27 A+/- 2 months. There was no significant difference in preoperative and postoperative urinary function. Fifty-one patients (96%) were sexually active preoperatively and were still sexually active postoperatively. Compared with the preoperative period, postoperative impairment of libido, erection, ejaculation, and orgasm were not significant. Every patient was able to achieve ejaculation after the intervention, and no retrograde ejaculations were reported. One patient was unable to have an erection after the intervention.Laparoscopic colorectal resection for diverticular disease does not significantly impair urinary and sexual function.

We extend a recent chiral approach to nuclear matter of Lutz et al. [Phys. Lett. B474 (2000) 7] by calculating the underlying (complex-valued) single-particle potential U(p,k_f) + i W(p,k_f). The potential for a nucleon at the bottom of the Fermi-sea, U(0,k_{f0})= - 20.0 MeV, comes out as much too weakly attractive in this approach. Even more seriously, the total single-particle energy does not rise monotonically with the nucleon momentum p, implying a negative effective nucleon mass at the Fermi-surface. Also, the imaginary single-particle potential, W(0,k_{f0}) = 51.1 MeV, is too large. More realistic single-particle properties together with a good nuclear matter equation of state can be obtained if the short range contributions of non-pionic origin are treated in mean-field approximation (i.e. if they are not further iterated with 1pi-exchange). We also consider the equation of state of pure neutron matter $bar E_n(k_n)$ and the asymmetry energy A(k_f) in that approach. The downward bending of these quantities above nuclear matter saturation density seems to be a generic feature of perturbative chiral pion-nucleon dynamics., 12 pages, 7 figures, submitted to Physical Review C

M-reps (formerly called DSLs) are a multiscale medial means for modeling and rendering 3D solid geometry. They are particularly well suited to model anatomic objects and in particular to capture prior geometric information effectively in deformable models segmentation approaches. The representation is based on figural models, which define objects at coarse scale by a hierarchy of figures—each figure generally a slab representing a solid region and its boundary simultaneously. This paper focuses on the use of single figure models to segment objects of relatively simple structure. A single figure is a sheet of medial atoms, which is interpolated from the model formed by a net, i.e., a mesh or chain, of medial atoms (hence the name m-reps), each atom modeling a solid region via not only a position and a width but also a local figural frame giving figural directions and an object angle between opposing, corresponding positions on the boundary implied by the m-rep. The special capability of an m-rep is to provide spatial and orientational correspondence between an object in two different states of deformation. This ability is central to effective measurement of both geometric typicality and geometry to image match, the two terms of the objective function optimized in segmentation by deformable models. The other ability of m-reps central to effective segmentation is their ability to support segmentation at multiple levels of scale, with successively finer precision. Objects modeled by single figures are segmented first by a similarity transform augmented by object elongation, then by adjustment of each medial atom, and finally by displacing a dense sampling of the m-rep implied boundary. While these models and approaches also exist in 2D, we focus on 3D objects. The segmentation of the kidney from CT and the hippocampus from MRI serve as the major examples in this paper. The accuracy of segmentation as compared to manual, slice-by-slice segmentation is reported.

We extend a recent three-loop calculation of nuclear matter in the systematic framework of chiral perturbation theory to finite temperatures T. The contributions from one- and two-pion exchange diagrams which cause nuclear binding and saturation at T=0 are included for T>0 in the density and temperature dependent free energy per particle, $\bar F(rho,T)$. The so-called anomalous 2pi-exchange contribution $\bar A(rho,T)$ (with no counterpart in the ground state energy density at T=0) is consistently included. The calculated pressure isotherms display the familiar first-order liquid-gas phase transition of isospin symmetric nuclear matter with a critical point at T_c = 25.5 MeV and rho_c = 0.09 fm^{-3}. The too high value of the critical temperature originates from the strong momentum dependence of the underlying single-particle potential U(p,k_{f0}) near the Fermi-surface. We also consider pure neutron matter at T>0 in the same framework and find fair agreement with sophisticated many-body calculations for neutron densities rho_n < 0.2 fm^{-3}., 10 pages, 4 figures, submitted to Physics Letters B

Using the two-loop approximation of chiral perturbation theory, we calculate the momentum and density dependent single particle potential of nucleons in isospin-symmetric nuclear matter. The contributions from one- and two-pion exchange diagrams give rise to a potential depth for a nucleon at rest of $U(0,k_{f0}) = -53.2 $MeV at saturation density. The momentum dependence of the real part of the single particle potential $U(p,k_{f0})$ is non-monotonic and can be translated into a mean effective nucleon mass of $\bar M^* \simeq 0.8 M$. The imaginary part of the single particle potential $W(p,k_f)$ is generated to that order entirely by iterated one-pion exchange. The resulting half width of a nucleon hole-state at the bottom of the Fermi sea comes out as $W(0,k_{f0})=29.7 $MeV. The basic theorems of Hugenholtz-Van-Hove and Luttinger are satisfied in our perturbative two-loop calculation of the nuclear mean field., Comment: 13 pages, 5 figures, submitted to Nuclear Physics A

Primary malignant melanoma of the esophagus is a rare but aggressive tumor that accounts for less than 0.1-0.2% of all esophageal malignancies. The aim of this study was to report a case of primary malignant melanoma of the esophagus in a 72-year-old woman. The diagnosis was histologically proven, but the patient died despite extensive surgical resection.

The prevalence of GB virus C (GBV-C)/ hepatitis G virus (HGV) RNA and antibodies to the structural E2 protein was investigated in a cohort of HIV-1 infected patients. Of 346 individuals, RNA was detected in 143 and E2 antibodies were detected in 73, for an overall prevalence of 62.4%. Intravenous drug use and homosexuality were identified as major transmission risk factors. GBV-C/HGV RNA prevalence was associated with hepatitis B coinfection, whereas antibodies to E2 were associated with older age and lower CD4+ cell counts. GBV-C/HGV infection was frequent in this group of HIV-infected patients and was associated with older age, lower CD4 + cell counts, and the presence of hepatitis B surface antigen.

Many transcription factors activate by directly interacting with RNA polymerase (RNAP). The C terminus of the RNAP α subunit (αCTD) is a common target of activators. We used both random mutagenesis and alanine scanning to identify αCTD residues that are crucial for MetR-dependent activation of metE and metH . We found that these residues localize to two distinct faces of the αCTD. The first is a complex surface consisting of residues important for α-DNA interactions, activation of both genes (residues 263, 293, and 320), and activation of either metE only (residues 260, 276, 302, 306, 309, and 322) or metH only (residues 258, 264, 290, 294, and 295). The second is a distinct cluster of residues important for metE activation only (residues 285, 289, 313, and 314). We propose that a difference in the location of the MetR binding site for activation at these two promoters accounts for the differences in the residues of α required for MetR-dependent activation. We have designed an in vitro reconstitution-purification protocol that allows us to specifically orient wild-type or mutant α subunits to either the β-associated or the β′-associated position within RNAP (comprising α 2 , β, β′, and ς subunits). In vitro transcriptions using oriented α RNAP indicate that a single αCTD on either the β- or the β′-associated α subunit is sufficient for MetR activation of metE , while MetR interacts preferentially with the αCTD on the β-associated α subunit at metH . We propose that the different αCTD requirements at these two promoters are due to a combination of the difference in the location of the activation site and limits on the rotational flexibility of the αCTD.

The correlation between response to antiviral therapy and pretreatment viral load in patients with chronic hepatitis C has prompted the development of quantitative assays to measure viral load. The aim of our study was to assess the clinical relevance of the newly developed semiautomated PCR system COBAS HCV MONITOR version 2.0 in comparison with (i) the AMPLICOR HCV MONITOR version 1.0 assay, which underestimates RNA concentration of hepatitis C virus (HCV) genotypes 2 to 6, and (ii) the QUANTIPLEX HCV RNA version 2.0 assay, which achieves equivalent quantification for each HCV genotype, with samples from 174 patients diagnosed with chronic hepatitis C before therapy. The level and range of quantification measured with AMPLICOR HCV MONITOR version 1.0 were 1 log lower than when measured with the COBAS HCV MONITOR version 2.0, at 0.261 × 10 6 RNA copies/ml (range, 0.001 × 10 6 to 2.50 × 10 6 RNA copies/ml) and 4.032 × 10 6 RNA copies/ml (range, 0.026 × 10 6 to 72.6 × 10 6 RNA copies/ml), respectively. The two assays showed a poor correlation ( r 2 = 0.175). The level and range of quantification were similar when measured with the COBAS HCV MONITOR version 2.0 and QUANTIPLEX HCV RNA version 2.0 assays, at 3.03 × 10 6 RNA copies/ml (range, 0.023 × 10 6 to 72.6 × 10 6 RNA copies/ml) and 4.91 Meq/ml (range, 0.200 to 49.5 Meq/ml), respectively. The two assays showed a strong correlation ( r 2 = 0.686) for each HCV genotype. The duration of treatment (6 or 12 months) is modulated according to HCV genotype and viral load. Our results indicate that COBAS HCV MONITOR version 2.0 and QUANTIPLEX HCV RNA version 2.0 assays showing an equal dynamic range for each HCV genotype are suitable tools to assess patients before therapy.

By means of neutron diffraction, a study has been made of the variation of the cationic distribution and short-range order in nickel-manganite ceramics Ni0.8Mn2.2O4, in relation with their thermal history. The thermal treatment of metallization which is an annealing at 850 °C followed by a quenching, induces a partial migration of Ni2+ ions from octahedral B to tetrahedral A sites of the cubic spinel structure and a decrease of the short-range order between nickel and manganese atoms on the B sites. These two effects increase the probability of the hopping of electrons from octahedral-site Mn3+ to octahedral-site Mn4+ and provide the major mechanism for the electrical conductivity increase associated with the thermal treatment of metallization of ceramics. La diffraction neutronique a permis d'etudier la variation de la distribution cationique et de l'ordre a courte distance dans les ceramiques de manganite de nickel Ni0,8Mn2,2O4, en relation avec leur histoire thermique. Le traitement thermique de metallisation, un recuit a 850 °C suivi d'une trempe, provoque une migration partielle des ions Ni2+ des sites octaedriques B vers les sites tetraedriques A de la structure cubique spinelle et une diminution de l'ordre a courte distance entre les atomes de nickel et de manganese sur les sites B. Ces deux effets augmentent la probabilite des sauts d'electrons entre les ions Mn3+ et les ions Mn4+ en sites B et rendent ainsi compte en grande partie de l'augmentation de conductivite electrique associee au traitement thermique de metallisation des ceramiques.

A model of object shape by nets of medial and boundary primitives is justified as richly capturing multiple aspects of shape and yet requiring representation space and image analysis work proportional to the number of primitives. Metrics are described that compute an object representation's prior probability of local geometry by reflecting variabilities in the net's node and link parameter values, and that compute a likelihood function measuring the degree of match of an image to that object representation. A paradigm for image analysis of deforming such a model to optimize a posteriori probability is described, and this paradigm is shown to be usable as a uniform approach for object definition, object-based registration between images of the same or different imaging modalities, and measurement of shape variation of an abnormal anatomical object, compared with a normal anatomical object. Examples of applications of these methods in radiotherapy, surgery, and psychiatry are given.

Prevalence of GBV-C/HGV was determined in a cohort of HIV-infected patients, via a reverse transcription-polymerase chain reaction detection of RNA in serum, amplifying the NS5 region of GBV-C/HGV genome. GBV-C/HGV RNA was detected in 143 (37.7%) of 379 patients, with similar results in the different HIV risk groups: 25/56 (44.6%) in intravenous drug users, 66/161 (41%) in homo- and bisexual men, 35/108 (32.4%) in heterosexual patients, 6/20 (30%) in transfusion recipients (P = 0.41). There was no difference according to the presence or absence of hepatitis C virus infection. In univariate analysis, GBV-C/HGV genome prevalence was lower in patients over 50 years old (18.2%), compared to other age groups (20-29 years: 34.2%; 30-39 years: 44.3%; 40-49 years: 36.7%, P = 0.03), as well as in patients with normal CD4 cell count (29.2% vs. 45.4% between 200-500/mm 3 , and 35.3% below 200 CD4/mm 3 , P = 0.012) and individuals with a chronic hepatitis B. However, in the multivariate analysis, the only prognostic factor of GBV-C/HGV RNA positivity was the presence of a chronic hepatitis B, compared to the absence of any HBV marker, or a previous exposition to HBV (presence of anti-HBc and/or anti-HBs, absence of HBsAg), or the presence of anti-HBs alone.

The structure and the microstructure of nickel manganite NTC thermistors have been determined and correlated with their electrical properties in order to understand the `ageing' phenomenon observed in these semiconductor devices. It has been shown that the heat treatment of metallization by serigraphy is responsible for structural and microstructural modifications. During this annealing some of the Ni 2+ cations migrate from the octahedral sites to the tetrahedral sites. At the same time, the ceramic is oxidized and precipitates of a cationic defect spinel phase appear. These modifications lead to a decrease in resistivity. During the ageing test at 125°C the cationic distribution does not change but the precipitates disappear. It induces an increase in resistivity. An improved serigraphy process is proposed to achieve stable NTC thermistors.

Jurors who are opposed to the death penalty are excluded from serving on trials in which the defendant may be sentenced to death. The exclusion of such jurors from death-penalty trials raises some concern about the fairness of these juries in deciding the guilt or innocence of a defendant. This article uses data from a survey of behaviors and beliefs of jurors conducted at the conclusion of non–capital offense trials to study this issue. A Bayesian hierarchical model is proposed for the probabilities of voting guilty or not guilty on a particular trial given various death-penalty beliefs. The Gibbs sampler is used to fit the model. The posterior distributions of the log odds of voting guilty for jurors who would be excluded from death-penalty juries versus those who would not be excluded suggest that there may be differences between the decisions of jurors on non–capital offense trials. We believe that they are likely to differ on death-penalty trials as well. The results from fitting the hierarc...

Believing that figural zoom invariance and the cross-figural boundary linking implied by medial loci are important aspects of object shape, we present the mathematics of and algorithms for the extraction of medial loci directly from image intensities. The medial loci called cores are defined as generalized maxima in scale space of a form of medial information that is invariant to translation, rotation, and, in particular, zoom. These loci are very insensitive to image disturbances, in strong contrast to previously available medial loci, as demonstrated in a companion paper. Core-related geometric properties and image object representations are laid out which, together with the aforementioned insensitivities, allow the core to be used effectively for a variety of image analysis objectives.

With the view of understanding the electrical conduction mechanism in the nickel-copper manganite spinels, the cation distribution and the ionic configurations of these compounds have been established by associating powder neutron diffraction, thermogravimetric measurements and XPS spectroscopy analysis. Neutron diffraction measurements allow us to reach the scattering lengths in both tetrahedral and octahedral sites. From this information we deduce lower and upper limits for the different cation fractions in both sites. The XPS spectroscopy analysis shows a predominately divalent copper, localized in tetrahedral sites. The monovalent copper is also present, but at a much smaller content. The additional information supplied by Mn 2+ tetrahedral thermogravimetric measurements resolves the cation distribution in these compounds. Finally, the discussion of the electrical properties using these structural formulas has shown that the presence of copper probably induces a mean-range hopping, the average distance of jumps being estimated to ≈ 9 A.