Pressure dependence of diffusion in simple glasses and supercooled liquids

Using molecular dynamics simulation, we have calculated the pressure dependence of the diffusion constant in a binary Lennard-Jones Glass. We observe four temperature regimes. The apparent activation volume drops from high values in the hot liquid to a plateau value. Near the critical temperature of the mode coupling theory it rises steeply, but in the glassy state we find again small values, similar to the ones in the liquid. The peak of the activation volume at the critical temperature is in agreement with the prediction of mode coupling theory

Prevalence and severity of mental disorders in military personnel: a standardised comparison with civilians

Aims. Provision and need for mental health services among military personnel are a major concern across nations. Two recent comparisons suggest higher rates of mental disorders in US and UK military personnel compared with civilians. However, these findings may not apply to other nations. Previous studies have focused on the overall effects of military service rather than the separate effects of military service and deployment. This study compared German military personnel with and without a history of deployment to sociodemographically matched civilians regarding prevalence and severity of 12-month DSM-IV mental disorders. Method. 1439 deployed soldiers (DS), 779 never deployed soldiers (NS) and 1023 civilians were assessed with an adapted version of the Munich Composite International Diagnostic interview across the same timeframe. Data were weighted using propensity score methodology to assure comparability of the three samples. Results. Compared with adjusted civilians, the prevalence of any 12-month disorder was lower in NS (OR: 0.7, 95% CI: 0.5–0.99) and did not differ in DS. Significant differences between military personnel and civilians regarding prevalence and severity of individual diagnoses were only apparent for alcohol (DS: OR: 0.3, 95% CI: 0.1–0.6; NS: OR: 0.2, 95% CI: 0.1–0.6) and nicotine dependence (DS: OR: 0.5, 95% CI: 0.3–0.6; NS: OR: 0.5, 95% CI: 0.3–0.7) with lower values in both military samples. Elevated rates of panic/agoraphobia (OR: 2.7, 95% CI: 1.4–5.3) and posttraumatic stress disorder (OR: 3.2, 95% CI: 1.3–8.0) were observed in DS with high combat exposure compared with civilians. Conclusions. Rates and severity of mental disorders in the German military are comparable with civilians for internalising and lower for substance use disorders. A higher risk of some disorders is reduced to DS with high combat exposure. This finding has implications for mental health service provision and the need for targeted interventions. Differences to previous US and UK studies that suggest an overall higher prevalence in military personnel might result from divergent study methods, deployment characteristics, military structures and occupational factors. Some of these factors might yield valuable targets to improve military mental health

Coherent instabilities in a semiconductor laser with fast gain recovery

We report the observation of a coherent multimode instability in quantum cascade lasers (QCLs), which is driven by the same fundamental mechanism of Rabi oscillations as the elusive Risken-Nummedal-Graham-Haken (RNGH) instability predicted 40 years ago for ring lasers. The threshold of the observed instability is significantly lower than in the original RNGH instability, which we attribute to saturable-absorption nonlinearity in the laser. Coherent effects, which cannot be reproduced by standard laser rate equations, can play therefore a key role in the multimode dynamics of QCLs, and in lasers with fast gain recovery in general.Comment: 5 pages, 4 figure

Fast-forwarding evolution—Accelerated adaptation in a proofreading-deficient hypermutator herpesvirus

Evolution relies on the availability of genetic diversity for fitness-based selection. However, most deoxyribonucleic acid (DNA) viruses employ DNA polymerases (Pol) capable of exonucleolytic proofreading to limit mutation rates during DNA replication. The relative genetic stability produced by high-fidelity genome replication can make studying DNA virus adaptation and evolution an intensive endeavor, especially in slowly replicating viruses. Here, we present a proofreading-impaired Pol mutant (Y547S) of Marek’s disease virus that exhibits a hypermutator phenotype while maintaining unimpaired growth in vitro and wild-type (WT)-like pathogenicity in vivo. At the same time, mutation frequencies observed in Y547S virus populations are 2–5-fold higher compared to the parental WT virus. We find that Y547S adapts faster to growth in originally non-permissive cells, evades pressure conferred by antiviral inhibitors more efficiently, and is more easily attenuated by serial passage in cultured cells compared to WT. Our results suggest that hypermutator viruses can serve as a tool to accelerate evolutionary processes and help identify key genetic changes required for adaptation to novel host cells and resistance to antiviral therapy. Similarly, the rapid attenuation achieved through adaptation of hypermutators to growth in cell culture enables identification of genetic changes underlying attenuation and virulence, knowledge that could practically exploited, e.g. in the rational design of vaccines

Multi-Particle Collision Dynamics -- a Particle-Based Mesoscale Simulation Approach to the Hydrodynamics of Complex Fluids

In this review, we describe and analyze a mesoscale simulation method for fluid flow, which was introduced by Malevanets and Kapral in 1999, and is now called multi-particle collision dynamics (MPC) or stochastic rotation dynamics (SRD). The method consists of alternating streaming and collision steps in an ensemble of point particles. The multi-particle collisions are performed by grouping particles in collision cells, and mass, momentum, and energy are locally conserved. This simulation technique captures both full hydrodynamic interactions and thermal fluctuations. The first part of the review begins with a description of several widely used MPC algorithms and then discusses important features of the original SRD algorithm and frequently used variations. Two complementary approaches for deriving the hydrodynamic equations and evaluating the transport coefficients are reviewed. It is then shown how MPC algorithms can be generalized to model non-ideal fluids, and binary mixtures with a consolute point. The importance of angular-momentum conservation for systems like phase-separated liquids with different viscosities is discussed. The second part of the review describes a number of recent applications of MPC algorithms to study colloid and polymer dynamics, the behavior of vesicles and cells in hydrodynamic flows, and the dynamics of viscoelastic fluids

In situ quantification of HER2–protein tyrosine kinase 6 (PTK6) protein–protein complexes in paraffin sections from breast cancer tissues

BACKGROUND: Protein tyrosine kinase 6 (PTK6; breast tumour kinase) is overexpressed in up to 86% of the invasive breast cancers, and its association with the oncoprotein human epidermal growth factor receptor 2 (HER2) was shown in vitro by co-precipitation. Furthermore, expression of PTK6 in tumours is linked with the expression of HER2. METHOD AND RESULTS: In this study, we used the proximity ligation assay (PLA) technique on formalin-fixed paraffin sections from eighty invasive breast carcinoma tissue specimens to locate PTK6-HER2 protein-protein complexes. Proximity ligation assay signals from protein complexes were assessed quantitatively, and expression levels showed a statistically significant association with tumour size (P=0.015) and course of the cancer disease (P=0.012). CONCLUSION: Protein tyrosine kinase 6 forms protein complexes with HER2 in primary breast cancer tissues, which can be visualised by use of the PLA technique. Human epidermal growth factor receptor 2-PTK6 complexes are of prognostic relevance

Current practices in long-term video-EEG monitoring services: A survey among partners of the E-PILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery.

The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement. Complete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patient's ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros. This study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe

Specific phobia predicts psychopathology in young women

Contains fulltext : 90255.pdf (publisher's version ) (Closed access)Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Data came from the Dresden Predictor Study in which 1,538 German women (18-25 years) completed a diagnostic interview at two time points. Women with specific phobia had a twofold increase in odds of developing any anxiety disorder, generalized anxiety disorder, depression, and any somatoform disorder during 17 months, compared to women without specific phobia. Except for depression, these associations persisted after adjustment for all comorbid mental disorders. Specific phobia thus appears to be a risk factor for a variety of problems. The result further underpins the necessity for early intervention for specific phobia to prevent later mental health problems

Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial

Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m−2) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m−2) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4–6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m−2 plus CI-5FU 225 mg m−2 was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39–82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m−2 plus CI-5FU 225 mg m−2 with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC