Reduced Sensitivity to Charge Noise in Semiconductor Spin Qubits via Symmetric Operation.

We demonstrate improved operation of exchange-coupled semiconductor quantum dots by substantially reducing the sensitivity of exchange operations to charge noise. The method involves biasing a double dot symmetrically between the charge-state anticrossings, where the derivative of the exchange energy with respect to gate voltages is minimized. Exchange remains highly tunable by adjusting the tunnel coupling. We find that this method reduces the dephasing effect of charge noise by more than a factor of 5 in comparison to operation near a charge-state anticrossing, increasing the number of observable exchange oscillations in our qubit by a similar factor. Performance also improves with exchange rate, favoring fast quantum operations.

Multicentric performance analysis of HCV quantification assays and its potential relevance for HCV treatment.

An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1-47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1-21.0 % and CTM v2: 15.0-32.3 %; CVs at 25 IU/ml: RealTime 17.6-34.9 % and CTM v2 28.2-54.9 %). These findings confirm the superior precision of RealTime versus CTM v2 at low-level viremia even across different laboratories including the new clinical decision point at 25 IU/ml. A highly precise monitoring of HCV viral load during therapy will remain crucial for patient management with regard to futility rules, therapy efficacy and SVR.

Undoped accumulation-mode Si/SiGe quantum dots.

We report on a quantum dot device design that combines the low disorder properties of undoped SiGe heterostructure materials with an overlapping gate stack in which each electrostatic gate has a dominant and unique function-control of individual quantum dot occupancies and of lateral tunneling into and between dots. Control of the tunneling rate between a dot and an electron bath is demonstrated over more than nine orders of magnitude and independently confirmed by direct measurement within the bandwidth of our amplifiers. The inter-dot tunnel coupling at the [Formula: see text] charge configuration anti-crossing is directly measured to quantify the control of a single inter-dot tunnel barrier gate. A simple exponential dependence is sufficient to describe each of these tunneling processes as a function of the controlling gate voltage.

[Combined hepatitis A/B vaccination: evaluation of a vaccination schedule in facilities for handicapped people]. / Hepatitis A/B-Kombinationsimpfung: Evaluation eines Impfprogramms in Werkstätten für Menschen mit Behinderung.

AIM OF THE STUDY: People with mental and physical disabilities have a higher risk of infection with hepatitis viruses. Studies conducted so far show contradictory results on the success of vaccination in this population. These people live and work under special conditions and sometimes have immune defects. METHODS: We investigated the antibody response after combined vaccination against hepatitis A and B in facilities for handicapped people in the city of Essen/Germany. Antibodies were determined in people with disabilities (n=949) and also in social workers taking care of handicapped people (n=115). RESULTS: Protective antibodies against hepatitis A were detected in 98.9% in people with disabilities and social workers. The seroconversion rate against hepatitis B in handicapped people was 90.2% and was comparable to the seroconversion rate in social workers (91.3%). Re-vaccinations were offered to all people with anti-HBs titres below 100 IU/L (28% of handicapped and 23.5% of social workers). In the group of low responders in handicapped people about 50% developed anti-HBs concentration above 100 IU/L. Non-responders showed 30-40% seroconversion rate after re-vaccination. CONCLUSION: Based on this study we would recommend serological tests about 4-8 weeks after vaccination to confirm seroconversion. By this procedure people who need a booster vaccination will be recognized and non-responders should be offered another HBV vaccination. In about 20% of the non-responders included in this study HBs antigen was detected.

[Epidemiology of hepatitis A, B, and C among adults in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)]. / Die Seroepidemiologie der Hepatitis A, B und C in Deutschland: Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1).

Ten years after seroepidemiological data were obtained in the German National Health Interview and Examination Survey 1998 (GNHIES98), German Health Interview and Examination Survey (DEGS1) data contribute to a population-based, representative surveillance of hepatitis A and B immunity and of the serological markers for hepatitis C in Germany. The prevalence of antibodies against the hepatitis A virus is 48.6 %. In comparison to the situation 10 years ago, seroprevalence is significantly higher among 18- to 39-year-old adults and is significantly lower in those aged 50-79 years. The association between age and seroprevalence has changed, indicating a decrease in naturally acquired hepatitis A immunity. Individual and population immunity has to be achieved through vaccination. Prevalence of hepatitis B antibodies indicates that 5.1 % of adults have been exposed to the virus, significantly fewer than 10 years ago (7.9 %). Prevalence of hepatitis B surface antibodies indicates that 22.9 % of adults have been vaccinated against hepatitis B. Vaccination coverage has increased in all age groups and is highest in the younger age groups. These positive trends can be attributed to the general recommendation since 1995 to vaccinate against hepatitis B. For hepatitis C, the prevalence of antibodies in the general population is 0.3 %. Germany thus remains a low-HCV-endemic country. An English full-text version of this article is available at SpringerLink as supplemental.

Coherent singlet-triplet oscillations in a silicon-based double quantum dot.

Silicon is more than the dominant material in the conventional microelectronics industry: it also has potential as a host material for emerging quantum information technologies. Standard fabrication techniques already allow the isolation of single electron spins in silicon transistor-like devices. Although this is also possible in other materials, silicon-based systems have the advantage of interacting more weakly with nuclear spins. Reducing such interactions is important for the control of spin quantum bits because nuclear fluctuations limit quantum phase coherence, as seen in recent experiments in GaAs-based quantum dots. Advances in reducing nuclear decoherence effects by means of complex control still result in coherence times much shorter than those seen in experiments on large ensembles of impurity-bound electrons in bulk silicon crystals. Here we report coherent control of electron spins in two coupled quantum dots in an undoped Si/SiGe heterostructure and show that this system has a nuclei-induced dephasing time of 360 nanoseconds, which is an increase by nearly two orders of magnitude over similar measurements in GaAs-based quantum dots. The degree of phase coherence observed, combined with fast, gated electrical initialization, read-out and control, should motivate future development of silicon-based quantum information processors.

What is vinculin needed for in platelets?

UNLABELLED: Summary. BACKGROUND: Vinculin links integrins to the cell cytoskeleton by virtue of its binding to proteins such as talin and F-actin. It has been implicated in the transmission of mechanical forces from the extracellular matrix to the cytoskeleton of migrating cells. Vinculin's function in platelets is unknown. OBJECTIVE: To determine whether vinculin is required for the functions of platelets and their major integrin, α(IIb) ß(3) . METHODS: The murine vinculin gene (Vcl) was deleted in the megakaryocyte/platelet lineage by breeding Vcl fl/fl mice with Pf4-Cre mice. Platelet and integrin functions were studied in vivo and ex vivo. RESULTS: Vinculin was undetectable in platelets from Vcl fl/fl Cre(+) mice, as determined by immunoblotting and fluorescence microscopy. Vinculin-deficient megakaryocytes exhibited increased membrane tethers in response to mechanical pulling on α(IIb) ß(3) with laser tweezers, suggesting that vinculin helps to maintain membrane cytoskeleton integrity. Surprisingly, vinculin-deficient platelets displayed normal agonist-induced fibrinogen binding to α(IIb) ß(3) , aggregation, spreading, actin polymerization/organization, clot retraction and the ability to form a procoagulant surface. Furthermore, vinculin-deficient platelets adhered to immobilized fibrinogen or collagen normally, under both static and flow conditions. Tail bleeding times were prolonged in 59% of vinculin-deficient mice. However, these mice exhibited no spontaneous bleeding and they formed occlusive platelet thrombi comparable to those in wild-type littermates in response to carotid artery injury with FeCl(3) . CONCLUSION: Despite promoting membrane cytoskeleton integrity when mechanical force is applied to α(IIb) ß(3) , vinculin is not required for the traditional functions of α(IIb) ß(3) or the platelet actin cytoskeleton.

Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus.

BACKGROUND: This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. METHODS: Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. RESULTS: Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated approximately 20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic disease. Another kidney recipient was treated 7 weeks before he died. The cerebrospinal fluid viral load remained at constant low levels (<10,000 copies/mL) for approximately 5 weeks; it increased suddenly by almost 5 orders of magnitude thereafter. After death, no virus was found in peripheral compartments (nerve tissue, heart, liver, or the small intestine) in this patient, in contrast to in patients in the same cohort who died early. CONCLUSIONS: Our report includes, to our knowledge, the longest documented treatment course of symptomatic rabies and the first time that the virus concentration was measured over time and in different body compartments. The postmortem virus concentration in the periphery was low, but there was no evidence of a reduction of virus in the brain.

Analytical performance characteristics and clinical utility of a novel assay for total hepatitis C virus core antigen quantification.

The detection and quantification of hepatitis C virus (HCV) core antigen in serum or plasma by the use of different assay formats have previously been shown to represent useful markers of viral replication. In the present study, the intrinsic performance characteristics and the potential clinical utility of a novel assay for the quantification of total HCV core antigen were comprehensively assessed by using clinical serum samples and specimens contained in various evaluation panels. The Architect HCV Ag assay showed a specificity of 100%. The intra- and interassay coefficients of variation ranged from 3.6 to 8.0% and from 4.7 to 9.5%, respectively. Except for HCV genotype 2 isolates, the analytical sensitivity was always less than 10 fmol core antigen/liter, corresponding to approximately 500 to 3,000 IU of HCV RNA/ml. Linearity was guaranteed throughout the dynamic range (10 to 20,000 fmol/liter). When seroconversion panels were tested, the assay was not inferior to HCV RNA detection and reduced the preseroconversion period by 4 to 16 days. The results obtained by core antigen and HCV RNA quantification for 385 clinical specimens were correlated by regression analysis (r = 0.857), but the calculated conversion equation differed significantly from the line of identity. Monitoring of viral kinetics by use of either core antigen or RNA concentrations in 38 HCV-infected patients undergoing antiviral combination therapy resulted in very similarly shaped curves in all cases. Finally, the Architect HCV Ag assay was also shown to enable high-throughput screening of in vitro HCV RNA replication. With these results taken together, the Architect HCV Ag assay proved to be a specific, reproducible, highly sensitive, and clinically applicable test format which will find its future place in the context of virological HCV diagnostics.

Lack of de novo hepatitis C virus infections and absence of nosocomial transmissions of GB virus C in a large cohort of German haemodialysis patients.

To determine the prevalence and incidence of hepatitis C virus (HCV) infections among haemodialysis patients, a large prospective multicentre trial was conducted in the German Federal State of North Rhine-Westphalia. Sera obtained from the recruited patients in two separate sampling rounds run 1 year apart were analysed for both anti-HCV antibodies and HCV RNA. HCV RNA positive samples were also genotyped by direct sequencing of an HCV core fragment. In the first and second rounds, 150 (5.2%) of 2909 and 114 (5.4%) of 2100 patients were anti-HCV positive, respectively, and 4% of individuals were viraemic. Evaluation of potential risk factors in a case-control study indicated that the factors 'foreign country of birth', 'blood transfusions given before 1991' and 'duration of treatment on haemodialysis' were associated with the risk of HCV infection. Among the 2100 patients of whom 'paired' serum samples from both rounds were available for testing, not a single 'de novo' HCV infection could be recorded. The fact that in a subset of about 20% of these patients no nosocomial GB virus C (GBV-C) transmission occurred during the observational period suggests that the lack of HCV seroconversions was not only attributable to the isolation of HCV-infected patients but also to the strict adherence to so-called universal hygienic precautions for infection control maintained in the participating dialysis centres.

Transmission of hepatitis C virus in an orthopedic hospital ward.

Healthcare-associated infections with hepatitis C virus (HCV) hitherto have been observed mainly in hemodialysis settings as well as in hematology and oncology wards. In this communication, molecular and epidemiologic investigations to elucidate an HCV outbreak in an orthopedic ward are reported. One hundred and thirty-five patients hospitalized in the ward and 104 staff members were tested. In addition to extensive epidemiologic reviews and hygienic inspections, direct sequencing of HCV PCR fragments and phylogenetic analysis of more than 300 partial HCV sequences obtained by end-point limiting-dilution real-time PCR assay were carried out. Six patients were infected with very closely related HCV variants. Patient-to-patient spread of the virus was inferred to have started from one patient with previous HCV infection to the other five patients during their hospital stay. Inspections did not reveal substantial breaches in basic infection control practices and did not identify a specific activity that might have led to nosocomial transmission. As a result of the investigations, the hospital corrected the documentation of all medical and nursing activities undertaken in the ward, abandoned the use of all multidose saline and other medication vials, and included explicitly recommendations for the safe preparation and administration of injectable drugs into internal infection control guidelines. Thereafter, no further nosocomial transmissions of HCV have been recorded in the orthopedic ward. The events observed suggest that nosocomial transmission of HCV is not limited to hemodialysis, hematology or oncology settings, and they also reinforce the mandatory adherence to basic infection control practices.

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting.

Both norepinephrine and acetylcholine have been shown to be critically involved in mediating attention but there remains debate about whether they serve similar or unique functions. Much of what is known about the role of these neurochemicals in cognition is based on manipulations done at the level of the cell body but these findings are difficult to reconcile with data regarding the unique contribution of cortical subregions, e.g. the dorsolateral prefrontal cortex, to attention. In the current study, we directly compared the effects of noradrenergic and cholinergic deafferentation of the rat medial prefrontal cortex, the homologue of primate dorsolateral prefrontal cortex, using an intradimensional/extradimensional attentional set shifting task, a task previously shown to be able to dissociate the function of the primate dorsolateral prefrontal cortex from orbitofrontal cortex. We found that noradrenergic, but not cholinergic, deafferentation produces specific impairments in the ability to shift attentional set. We also clarified the nature of the attentional deficits by assessing the ability of rats to disregard irrelevant stimuli. Noradrenergic lesions did not alter the ability of rats to ignore irrelevant stimuli, suggesting that the attentional deficit results from an overly focused attentional state that retards learning that a new stimulus dimension predicts reward.

Outcome of an exercise to notify patients treated by a general surgeon infected with the hepatitis C virus.

BACKGROUND: Health-care workers infected with the hepatitis C virus (HCV) and performing exposure-prone procedures may expose their patients to the risk of nosocomial HCV infection. OBJECTIVE: To assess the number of provider-to-patient transmissions of HCV among former patients of an HCV-infected general surgeon. RESULTS: The notification exercise covered 1461 individuals, on whom the surgeon performed 1683 operations. Eighty-two percent of these patients were tested for markers of HCV infection, and all but six subjects turned out to be not infected with the virus. Two of the anti-HCV positive patients were already infected before their operations, one individual was not available for further molecular analyses, and three subjects harboured HCV isolates that belonged to a different subtype (i.e. 1b) than the variant detected in the surgeon's serum. CONCLUSION: In this retrospective survey, no provider-to-patient transmission of HCV was detected among 1192 former patients of an infected general surgeon. This finding, one more time, suggests that such nosocomial transmission events are probably very rare. Consequently, recommendations for the management and guidance of HCV-infected health-care workers should carefully balance the workers' rights against justified patients' interests.

Towards a better resolution of hepatitis C virus variants: CLIP sequencing of an HCV core fragment and automated assignment of genotypes and subtypes.

Commercially available assays for typing of hepatitis C virus (HCV) isolates satisfy the current clinical needs. They are, however, limited in their ability to identify the multitude of existing HCV subtypes correctly. Therefore, these kits should only be used cautiously in epidemiological studies and will also not meet future clinical demands which might arise, e.g., from the application of HCV subtype-specific antiviral compounds. In an attempt to overcome the drawbacks of commercial typing procedures based on the analysis of the 5' untranslated region (5' UTR), an approach was developed which relies on CLIP sequencing of an HCV core fragment with automated assignments of types and subtypes via an originally created "core-specific" sequence database. The performance characteristics of the new technique were evaluated in comparison to the Trugene 5' NC Genotyping Kit. The core-based sequencing method could regularly detect HCV isolates of genotypes 1-6 with an analytical sensitivity of 5000 IU/ml. The accuracy of typing results obtained by the Trugene test was 97% (genotypes) and 81% (subtypes). The core-linked approach classified all HCV strains correctly on the level of genotypes and led to an adequate subtype assignment in 96% of all cases. This analytical performance characteristics recorded for the newly devised typing technique was superior to those reported for all commercially available assays, including a most recently released new generation of the line probe assay. Consequently, CLIP sequencing of an HCV core fragment with subsequent automated assignment of types and subtypes can be confidently used in clinical laboratory practice to answer current and also future questions in the context of HCV typing.

Evidence for a complex mosaic genome pattern in a full-length hepatitis C virus sequence.

The genome of the hepatitis C virus (HCV) exhibits a high genetic variability. This remarkable heterogeneity is mainly attributed to the gradual accumulation of mutational changes, whereas the contribution of recombination events to the evolution of HCV remains controversial so far. While performing phylogenetic analyses including a large number of sequences deposited in the GenBank, we encountered a full-length HCV sequence (AY651061) that showed evidence for inter-subtype recombination and was, therefore, subjected to a detailed analysis of its molecular structure. The obtained results indicated that AY651061 does not represent a "simple" HCV 1c isolate, but a complex 1a/1c mosaic genome, showing five putative breakpoints in the core to NS3 regions. To our knowledge, this is the first report on a mosaic HCV full-length sequence with multiple breakpoints. The molecular structure of AY651061 is reminiscent of complex homologous recombinant variants occurring among other members of the flaviviridae family, e.g. GB virus C, dengue virus, and Japanese encephalitis virus. Our finding of a mosaic HCV sequence may have important implications for many fields of current HCV research which merit careful consideration.

[Nosocomial transmission of viruses to pregnant women by infected medical personnel]. / Ubertragung wichtiger schwangerschaftsrelevanter Virusinfektionen durch medizinisches Personal.

Virus-infected medical personnel under certain circumstances might represent a risk for pregnant women. With regard to such nosocomial provider-to-patient transmissions, the pathogens rubella virus, herpes viruses and the hepatitis B and hepatitis C viruses are of particular concern. It will become clear from the following short communication that in this context one should strive to achieve optimal protection for the expectant mothers without restricting the professional activities of virus-infected members of the medical staff in an unjustified way. In this respect it always has to be kept in mind that the risk of provider-to-patient transmissions of viruses in obstetrics and neonatology can be significantly reduced by vaccinating all personnel working in these departments against infections by the rubella, varicella-zoster, and hepatitis B viruses, and that additional strict adherence to so-called universal hygienic precautions will add more than an incremental benefit.

Transcription-mediated amplification linked to line probe assay as a routine tool for HCV typing in clinical laboratories.

Typing of hepatitis C virus (HCV) isolates is currently a prerequisite for adequate tailoring of antiviral combination therapy. In many diagnostic laboratories, there seems to be a tendency toward convenient and time-saving procedures utilizing amplification products, which are already available from preceding qualitative or quantitative HCV ribonucleic acid (RNA) assays. In this context, we evaluated the performance characteristics of a combination of techniques, i.e., transcription-mediated amplification-line probe assay (TMA-LiPA), which links highly sensitive TMA of HCV RNA to the VERSANT HCV Genotype Assay (version 1). A total of 100 clinical samples were genotyped by TMA-LiPA. The obtained results were compared to those recorded by the original, nested reverse transcription (RT)-polymerase chain reaction (PCR)-based VERSANT assay, the core-related GEN-ETI-K DEIA, and phylogenetic analyses of partial sequences from the HCV core and NS5B regions. TMA-LiPA assigned the correct genotype to all 100 HCV isolates. For subtyping of genotype 1 and 2 isolates, TMA-LiPA only showed discriminatory powers of 82% and 53%, respectively. Thus, TMA-LiPA in our hands turned out as a convenient and time-saving routine procedure for HCV typing which currently provides sufficient information for clinical purposes. Like all 5'untranslated region (UTR)-based assays, the technique is limited, however, in its potentials to resolve the complexity of existing HCV subtypes.

Genotyping of hepatitis C virus isolates by a new line probe assay using sequence information from both the 5'untranslated and the core regions.

The correct assessment of hepatitis C virus (HCV) genotypes and subtypes by commercial assays is of utmost importance mainly for the therapeutic management of patients suffering from HCV infections. In this study, the performance characteristics of a newly designed genotyping assay were evaluated that does not rely exclusively on sequence information derived from the 5'untranslated region but also takes into account part of the HCV core. One hundred and ten clinical specimens were tested by this new assay prior to its commercialisation. The obtained typing results were compared to those recorded by the 5'UTR-based Versant HCV Genotyping Assay, version 1, the core-related Gen-Eti K DEIA, and phylogenetic analyses of partial HCV core and NS5B sequences. The HCV genotypes and subtypes identified by the newly devised kit were completely in line with the assignments achieved by DEIA and phylogenetic analyses. In particular, all 64 HCV strains belonging to subtypes 1a or 1b were recognised correctly, and HCV 6e and 6f isolates were adequately assigned to subtypes 6c-l. Thus, the second generation of the Versant genotyping assay could overcome the drawbacks of its exclusively 5'UTR-based predecessor and will turn out to be a reliable tool for HCV typing in clinical laboratories.

First case of hepatitis C virus transmission by a red blood cell concentrate after introduction of nucleic acid amplification technique screening in Germany: a comparative study with various assays.

BACKGROUND AND OBJECTIVES: Pooled nucleic acid amplification techniques (NAT) and donor screening for anti-hepatitis C virus (HCV) have reduced the diagnostic window period of HCV infection in the blood donor population from about 12 to 1 or 2 weeks. During that time, HCV RNA is hardly detectable by pooled or individual donation NAT. Here we describe a case of transfusion-acquired HCV infection from an extremely low-titre donation. After a repeat donor tested positive for HCV, a look-back procedure was initiated. A recipient of a red cell concentrate from the previous donation was identified and found to be infected with HCV as well. We compared several commercial NAT systems for their ability to detect the viraemic plasma. MATERIALS AND METHODS: Molecular analyses of HCV in donor and recipient samples were performed. The HCV-transmitting plasma was tested using different commercially available qualitative and quantitative NAT assays. RESULTS: HCV transmission was verified by molecular analyses and was assigned to genotype 2b. NAT with various commercial HCV assays detected the infection erratically in individual donations. However, the detection rate was not directly related to the claimed sensitivity of some HCV NATs. CONCLUSIONS: HCV transmission can be caused by donations that escape NAT detection even when tested in an individual donation. Comparison of different assays led to results that did not necessarily reflect the expected sensitivities. The need for standard materials representing further HCV genotypes is discussed.