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Biomedical subjects

P Samuelsson

Publications and source records attributed to P Samuelsson.

At least 19 recordsLinked to original sources

Full-counting statistics for voltage and dephasing probes.

We present a stochastic path integral method to calculate the full-counting statistics of conductors with energy conserving dephasing probes and dissipative voltage probes. The approach is explained for the experimentally important case of a Mach-Zehnder interferometer, but is easily generalized to more complicated setups. For all geometries where dephasing may be modeled by a single one-channel dephasing probe we prove that our method yields the same full-counting statistics as phase averaging of the cumulant generating function.

Journal Article↗

Noise and full counting statistics of incoherent multiple Andreev reflection.

We present a general theory for the full counting statistics of multiple Andreev reflections in incoherent superconducting-normal-superconducting contacts. The theory, based on a stochastic path integral approach, is applied to a superconductor-double-barrier system. It is found that all cumulants of the current show a pronounced subharmonic gap structure at voltages V=2Delta/en. For low voltages V< or =3. We show that this low-voltage result holds for a large class of incoherent superconducting-normal-superconducting contacts.

Journal Article↗

Andreev reflection eigenvalue density in mesoscopic conductors.

The energy-dependent Andreev reflection eigenvalues determine the transport properties of normal-superconducting systems. We evaluate the eigenvalue density to get insight into the formation of resonant electron-hole transport channels. The circuit-theory-like method developed can be applied to any generic mesoscopic conductor or combinations thereof. We present the results for experimentally relevant cases of a diffusive wire and a double tunnel junction.

Journal Article↗

Two-particle Aharonov-Bohm effect and entanglement in the electronic Hanbury Brown-Twiss setup.

We analyze a Hanbury Brown-Twiss geometry in which particles are injected from two independent sources into a mesoscopic conductor in the quantum Hall regime. All partial waves end in different reservoirs without generating any single-particle interference; in particular, there is no single-particle Aharonov-Bohm effect. However, exchange effects lead to two-particle Aharonov-Bohm oscillations in the zero-frequency current cross correlations. We demonstrate that this is related to two-particle orbital entanglement, detected via violation of a Bell inequality. The transport is along edge states and only adiabatic quantum point contacts and normal reservoirs are employed.

Journal Article↗

Orbital entanglement and violation of Bell inequalities in mesoscopic conductors.

We propose a spin-independent scheme to generate and detect two-particle entanglement in a mesoscopic normal-superconductor system. A superconductor, weakly coupled to the normal conductor, generates an orbitally entangled state by injecting pairs of electrons into different leads of the normal conductor. The entanglement is detected via violation of a Bell inequality, formulated in terms of zero-frequency current cross correlators. It is shown that the Bell inequality can be violated for arbitrary strong dephasing in the normal conductor.

Journal Article↗

The host response to urinary tract infection.

The authors use the UTI model to identify basic mechanisms of disease pathogenesis, host response induction, and defense. Their studies hold the promise to provide a molecular and genetic explanation for susceptibility to UTI, and to offer more precise tools for diagnosis and therapy of these infections. There are few infections where the host response is understood in such detail and where pathologic host responses can be linked to distinct disease states. The susceptibility to UTI varies greatly in the population. The studies suggest that distinct molecular defects can cause the clinical entity of acute pyelonephritis with renal scarring, and suggest that the susceptibility to UTI in certain patient groups may have a genetic basis. In addition, the distinct signal transduction pathways explain the development of symptoms, and propose that defects in those signaling mechanisms may occur in patients with ABU. In the future, it may be useful to include these host response parameters in the diagnostic arsenal, to help in early detection of patients susceptible to recurrent UTI and renal scarring. These patients may then be offered therapies that strengthen their defense, and be offered close surveillance for recurrences and other complications.

Animals↗

Adaptive control of the nitrate level in an activated sludge process.

In an activated sludge process for nitrogen removal, nitrate may be reduced to nitrogen gas by facultative heterotrophic bacteria in an anoxic environment. In order to guarantee sufficient supplies of readily biodegradable carbon compounds, an external carbon source often needs to be added. In this paper, an automatic control strategy for controlling the nitrate level using an external carbon source is presented. The external carbon source is added in the first anoxic zone to control the nitrate concentration in the last anoxic zone. Key process parameters are estimated on-line for a simplified Activated Sludge Model No 1. The estimated parameters are used for updating a linear quadratic controller. The strategy is illustrated in a simulation study with realistic influent data and is shown to perform very well.

Bioreactors↗

Chaotic dot-superconductor analog of the Hanbury Brown-Twiss effect.

As an electrical analog of the optical Hanbury Brown-Twiss effect, we study current cross correlations in a chaotic quantum dot-superconductor junction. One superconducting and two normal reservoirs are connected via point contacts to a chaotic quantum dot. For a wide range of contact widths and transparencies, we find large positive current correlations. The positive correlations are generally enhanced by normal backscattering in the contacts. Moreover, for normal backscattering in the contacts, the positive correlations survive when suppressing the proximity effect in the dot with a weak magnetic field.

Journal Article↗

Victims of awareness.

BACKGROUND: Intraoperative awareness with explicit recall may be followed by long-lasting mental symptoms. However, the average risk for developing mental sequelae after awareness, and the average severity and the duration of symptoms has not previously been illustrated in a consecutive series of awareness cases. METHODS: Nine patients among 18 consecutive, prospectively identified cases of intraoperative awareness with recall could be located after approximately 2 years and agreed to an interview about possible persisting problems. RESULTS: Four of the nine interviewed patients were still severely disabled due to psychiatric/psychological sequelae. All of these patients had experienced anxiety during the period of awareness, but only one had complained about pain. Another three patients had less severe, transient mental symptoms, although they could cope with these in daily life. Two patients denied any sequelae from their awareness episode. CONCLUSIONS: Up to 3 weeks after their unsuccessful anesthetic, repeated information and discussions had been offered. Despite the fact that all patients at that time claimed to be satisfied with this management, and eventually considered no further contacts necessary, this was obviously inaccurate. Therefore, professional psychiatric assessment, treatment and long-term follow-up should constitute standard practice for all patients who have experienced intraoperative awareness.

Adult↗

Control of the aeration volume in an activated sludge process for nitrogen removal.

Biological nitrogen removal in an activated sludge process is obtained by two biological processes; nitrification and denitrification. Nitrifying bacteria need dissolved oxygen and a sufficiently large aeration volume for converting ammonium to nitrate in the wastewater. The objective of this paper is to develop an automatic control strategy for adjusting the aerated volume so that the effluent ammonium level can be kept close to a desired value despite major changes in the influent load. The strategy is based on applying exact linearization of the IAWO Activated Sludge Process Model No 1. Simulation results show that the suggested controller effectively attenuates process disturbances.

Automation↗

Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation.

Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative but expressed several TLR species including TLR4, and TLR4 protein was detected. Infection with P fimbriated bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did not involve the LPS-CD14 pathway and was independent of lipid A myristoylation, as shown by mutational inactivation of the msbB gene. Co-staining experiments revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell membrane. The results demonstrate that P fimbriae activate epithelial cells by means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for P fimbriae can recruit TLR4 as co-receptors.

Animals↗

The 'innate' host response protects and damages the infected urinary tract.

Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.

Animals↗

Feed-forward control of the external carbon flow rate in an activated sludge process.

Biological nitrogen removal in an activated sludge process is obtained by two biological processes: nitrification and denitrification. Denitrifying bacteria need sufficient amounts of readily metabolized carbon. The objective of this paper is to develop an automatic control strategy for adjusting the external carbon flow rate so that the nitrate concentration in the last anoxic compartment is kept at a low pre-specified level. A simple model based feed-forward control combined with a standard feedback PI controller is suggested. Simulation results show that the suggested controller, despite being simple, effectively attenuates process disturbances.

Automation↗

Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection.

Neutrophil migration to infected mucosal sites involves a series of complex interactions with molecules in the lamina propria and at the epithelial barrier. Much attention has focussed on the vascular compartment and endothelial cells, but less is known about the molecular determinants of neutrophil behavior in the periphery. We have studied urinary tract infections (UTIs) to determine the events that initiate neutrophil recruitment and interactions of the recruited neutrophils with the mucosal barrier. Bacteria activate a chemokine response in uroepithelial cells, and the chemokine repertoire depends on the bacterial virulence factors and on the specific signaling pathways that they activate. In addition, epithelial chemokine receptor expression is enhanced. Interleukin (IL)-8 and CXCR1 direct neutrophil migration across the epithelial barrier into the lumen. Indeed, mIL-8Rh knockout mice showed impaired transepithelial neutrophil migration, with tissue accumulation of neutrophils, and these mice developed renal scarring. They had a defective antibacterial defense and developed acute pyelonephritis with bacteremia. Low CXCR1 expression was also detected in children with acute pyelonephritis. These results demonstrate that chemokines and chemokine receptors are essential to orchestrate a functional antimicrobial defense of the urinary tract mucosa. Mutational inactivation of the IL-8R caused both acute disease and chronic tissue damage.

Animals↗

Awareness during anaesthesia: a prospective case study.

BACKGROUND: Patients who are given general anaesthesia are not guaranteed to remain unconscious during surgery. Knowledge about the effectiveness of current protective measures is scarce, as is our understanding of patients' responses to this complication. We did a prospective case study to assess conscious awareness during anaesthesia. METHODS: 11785 patients who had undergone general anaesthesia were interviewed for awareness on three occasions: before they left the post-anaesthesia care unit, and 1-3 days and 7-14 days after the operation. FINDINGS: We identified 18 cases of awareness and one case of inadvertent muscle blockade that had occurred before unconsciousness. Incidence of awareness was 0.18% in cases in which neuromuscular blocking drugs were used, and 0.10% in the absence of such drugs. 17 cases of awareness were identified at the final interview, but no more than 11 would have been detected if an interview had been done only when the patients left the post-anaesthesia care unit. Four non-paralysed patients recalled intraoperative events, but none had anxiety during wakefulness or had delayed neurotic symptoms. This finding contrasts with anaesthesia with muscle relaxants, during which 11 of 14 patients had pain, anxiety, or delayed neurotic symptoms. After repeated discussion and information, the delayed neurotic symptoms resolved within 3 weeks in all patients. Analysis of individual cases suggests that a reduced incidence of recall of intraoperative events would not be achieved by monitoring of end-tidal anaesthetic gas concentration or by more frequent use of benzodiazepines. INTERPRETATION: The inability to prevent awareness by conventional measures may advocate monitoring of cerebral activity by neurophysiological techniques. However, the sensitivity of such techniques is not known, and in the light of our findings, at least 861 patients would need to be monitored to avoid one patient from suffering due to awareness during relaxant anaesthesia.

Adult↗

Novel ribosomal mutations affecting translational accuracy, antibiotic resistance and virulence of Salmonella typhimurium.

Many mutations in rpsL cause resistance to, or dependence on, streptomycin and are restrictive (hyperaccurate) in translation. Dependence on streptomycin and hyperaccuracy can each be reversed phenotypically by mutations in either rpsD or rpsE. Such compensatory mutations have been shown to have a ram phenotype (ribosomal ambiguity), increasing the level of translational errors. We have shown recently that restrictive rpsL alleles are also associated with a loss of virulence in Salmonella typhimurium. To test whether ram mutants could reverse this loss of virulence, we have isolated a set of rpsD alleles in Salmonella typhimurium. We found that the rpsD alleles restore the virulence of strains carrying restrictive rpsL alleles to a level close to that of the wild type. Unexpectedly, three out of seven mutant rpsD alleles tested have phenotypes typical of restrictive alleles of rpsL, being resistant to streptomycin and restrictive (hyperaccurate) in translation. These phenotypes have not been previously associated with the ribosomal protein S4. Furthermore, all seven rpsD alleles (four ram and three restrictive) can phenotypically reverse the hyperaccuracy associated with restrictive alleles of rpsL. This is the first demonstration that such compensations do not require that the compensating rpsD allele has a ribosomal ambiguity (ram) phenotype.

Alleles↗

[Dosage of anesthetics--a tricky question].

The optimal dosage of anaesthetic agents may be difficult. Not only does the intensity of surgical stimuli vary during a surgical procedure, but drug sensitivity varies between subjects exposed to comparable stimuli. Moreover, clinically monitored body reactions do not always reflect the balance between central nervous system effects of the surgical stimuli and of the anaesthetic agent. Therefore, the specialist in anaesthesiology requires access to additional methods of monitoring to enable dosage to be optimised for each patient, minute by minute, thus improving the chances of maintaining an appropriate depth of anaesthesia. Two electro-encephalographic techniques are presented in the article, and aspects of under- and over-dosage of anaesthetic agents are discussed.

Anesthetics, General↗