Polymer ejection from strong spherical confinement

We examine the ejection of an initially strongly confined flexible polymer from a spherical capsid through a nanoscale pore. We use molecular dynamics for unprecedentedly high initial monomer densities. We show that the time for an individual monomer to eject grows exponentially with the number of ejected monomers. By measurements of the force at the pore we show this dependence to be a consequence of the excess free energy of the polymer due to confinement growing exponentially with the number of monomers initially inside the capsid. This growth relates closely to the divergence of mixing energy in the Flory-Huggins theory at large concentration. We show that the pressure inside the capsid driving the ejection dominates the process that is characterized by the ejection time growing linearly with the lengths of different polymers. Waiting time profiles would indicate that the superlinear dependence obtained for polymers amenable to computer simulations results from a finite-size effect due to the final retraction of polymers' tails from capsids.Comment: 6 pages, 9 figures, accepted for publication in Phys. Rev. E, increased readability from previous versio

Dynamics of polymer ejection from capsid

Polymer ejection from a capsid through a nanoscale pore is an important biological process with relevance to modern biotechnology. Here, we study generic capsid ejection using Langevin dynamics. We show that even when the ejection takes place within the drift-dominated region there is a very high probability for the ejection process not to be completed. Introducing a small aligning force at the pore entrance enhances ejection dramatically. Such a pore asymmetry is a candidate for a mechanism by which a viral ejection is completed. By detailed high-resolution simulations we show that such capsid ejection is an out-of-equilibrium process that shares many common features with the much studied driven polymer translocation through a pore in a wall or a membrane. We find that the escape times scale with polymer length, $\tau \sim N^\alpha$. We show that for the pore without the asymmetry the previous predictions corroborated by Monte Carlo simulations do not hold. For the pore with the asymmetry the scaling exponent varies with the initial monomer density (monomers per capsid volume) $\rho$ inside the capsid. For very low densities $\rho \le 0.002$ the polymer is only weakly confined by the capsid, and we measure $\alpha = 1.33$, which is close to $\alpha = 1.4$ obtained for polymer translocation. At intermediate densities the scaling exponents $\alpha = 1.25$ and $1.21$ for $\rho = 0.01$ and $0.02$, respectively. These scalings are in accord with a crude derivation for the lower limit $\alpha = 1.2$. For the asymmetrical pore precise scaling breaks down, when the density exceeds the value for complete confinement by the capsid, $\rho \gtrapprox 0.25$. The high-resolution data show that the capsid ejection for both pores, analogously to polymer translocation, can be characterized as a multiplicative stochastic process that is dominated by small-scale transitions.Comment: 10 pages, 6 figure

Organisational downsizing, sickness absence, and mortality: 10-town prospective cohort study

Objective To examine whether downsizing, the reduction of personnel in organisations, is a predictor of increased sickness absence and mortality among employees.Design Prospective cohort study over 7.5 years of employees grouped into categories on the basis of reductions of personnel in their occupation and workplace: no downsizing ( 18%).Setting Four towns in Finland.Participants 5909 male and 16 521 female municipal employees, aged 19-62 years, who kept their jobs.Main outcome measures Annual sickness absence rate based on employers' records before and after downsizing by employment contract; all cause and cause specific mortality obtained from the national mortality register.Results Major downsizing was associated with an increase in sickness absence (P for trend < 0.001) in permanent employees but not in temporary employees. The extent of downsizing was also associated with cardiovascular deaths (P for trend < 0.01) but not with deaths from other causes. Cardiovascular mortality was 2.0 (95% confidence interval 1.0 to 3.9) times higher after major downsizing than after no downsizing. Splitting the follow up period into two halves showed a 5.1 (1.4 to 19.3) times increase in cardiovascular mortality for major downsizing during the first four years after downsizing. The corresponding hazard ratio was 1.4 (0.6 to 3.1) during the second half of follow up.Conclusion Organisational downsizing may increase sickness absence and the risk of death from cardiovascular disease in employees who keep their jobs

Clinical Outcomes Associated With Melanocytic Lesions Assessed Via Ancillary Gene Expression Profiling (GEP)

Aims/Objectives: Compare GEP assay prediction of 434 melanocytic lesions with dermatopathologist interpretation. Methods: Sensitivity and specificity of assay were calculated based on disagreement of assay prediction with dermatopathologist interpretation. Histologic features were recorded in disagreeing cases. Results: Eighty-five percent of lesions (369/434) had sufficient RNA for scoring. 74.2% 274/369 lesions were classified as “benign”, 11.9% (44/369) “indeterminate”, and 13.8% (51/369) “malignant”. 38/51 of lesions rendered “malignant” by dermatopathologists were classified “malignant” by assay (sensitivity = 74.5%). Lesions rendered by assay as “benign” but “malignant” by dermatopathologists were more likely to have rarer cytologic features. (13/51) lesions rendered “malignant” by dermatopathologists were classified by assay as “benign,” (4/13) or “indeterminate” (9/13). 270/318 lesions rendered “benign” by dermatopathologists were “benign” by assay (specificity = 84.9%). Of 44/369 “indeterminate” lesions, dermatopathologists rendered 9/44

Web tension measurements in the paper mill

Web tension measuring methods and corresponding instruments have been evaluated at the Graphic Arts Laboratory of the VTT. Together with Valmet Paper Machinery, cross-web tension profiles have been studied in different paper machines and they have been compared to other profiles measured by the process control system in the paper machine. The role of the paper machine tension profile in winding and in paper customer rolls is outlined.The measuring techniques developed seemed to be practical and are from now on available to analyze the paper machine performance. The realized field measurements have shown quite even profiles in basis weight, dry weight and moisture, which are normally measured at the dry end of the paper machine. Web tension can show drastic variation across the web and especially web edges used to be problematic

Decreasing trend in the incidence of serious pneumonias in Finnish children with juvenile idiopathic arthritis

OBJECTIVES: Children with juvenile idiopathic arthritis (JIA) may be predisposed to serious pneumonia due to modern disease-modifying anti-rheumatic treatment. In this nationwide retrospective study with clinical data, we describe the pneumonia episodes among children with JIA. METHODS: Patients under 18 years of age with JIA and pneumonia during 1998-2014 were identified in the National Hospital Discharge Register in Finland. Each individual patient record was reviewed, and detailed data on patients with JIA and pneumonia were retrieved, recorded, and analyzed. If the patient was hospitalized or received intravenous antibiotics, the pneumonia was considered serious. RESULTS: There were 157 episodes of pneumonia among 140 children with JIA; 111 episodes (71%) were serious (80% in 1998-2006 and 66% in 2007-2014). The mean age of the patients was 9 years. Forty-eight percent had active JIA and 46% had comorbidities. Disease-modifying anti-rheumatic drugs (DMARD) were used at the time of 135 episodes (86%): methotrexate (MTX) by 62% and biologic DMARDs (bDMARD) by 30%. There was no significant difference in the use of bDMARDs, MTX and glucocorticoids between the patient groups with serious and non-serious pneumonia episodes. During six of the episodes, intensive care was needed. Two patients (1.3%) died, the remaining ones recovered fully. CONCLUSIONS: Although the incidence of pneumonia and the use of immunosuppressive treatment among children with JIA increased from 1998 to 2014, the proportion of serious pneumonias in these patients decreased. There was no significant difference in the use of anti-rheumatic medication between patients with serious and non-serious pneumonia.Key Points• The incidence of serious pneumonias decreased from 1998 to 2014 among children with juvenile idiopathic arthritis (JIA).• There was no significant difference in the use of the disease-modifying anti-rheumatic medication between JIA patients with serious and non-serious pneumonias.• Active JIA, comorbidities, and combination medication were associated with nearly half of the pneumonias.Peer reviewe

Superconducting NbN microstrip detectors

Superconducting NbN strip transmission line counters and coupling circuits were processed on silicon wafers using thin film techniques, and they were characterized with several methods to verify the design principles. The stripline circuits, designed using microwave design rules, were simulated using a circuit design tool enhanced to include modelling of the superconducting lines. The strips, etched out of the 282 nm thick top NbN film with resistivity 284 µ?cm at 20 K, have critical temperatures in the range 12 to 13 K and a critical current density approximately Jc(0) = 3.3·105 A/cm2. The linearized heat transfer coefficient between the strip and the substrate is approximately 1.1·105 W/(m2K) and the healing length is about 1.6 µm between 3 and 5 K temperatures. Traversing 5 MeV a-particles caused the strips to quench. No events due to electrons could be detected in agreement with the predicted signal amplitude which is below the noise threshold of our wideband circuitry. The strip bias current and hence the signal amplitude were limited due to a microbridge at the isolator step of the impedance transformer

Dynamics of forced biopolymer translocation

We present results from our simulations of biopolymer translocation in a solvent which explain the main experimental findings. The forced translocation can be described by simple force balance arguments for the relevant range of pore potentials in experiments and biological systems. Scaling of translocation time with polymer length varies with pore force and friction. Hydrodynamics affects this scaling and significantly reduces translocation times.Comment: Published in: http://www.iop.org/EJ/article/0295-5075/85/5/58006/epl_85_5_58006.htm

Association of income and educational levels on initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study

Aims: Socioeconomic disparities have been reported in the outcomes of patients with atrial fibrillation (AF). We assessed the hypothesis that AF patients with higher income or educational level are more frequently initiated with oral anticoagulant (OAC) therapy for stroke prevention.Methods: The nationwide registry-based Finnish AntiCoagulation in Atrial Fibrillation cohort covers all patients with AF from all levels of care in Finland. Patients were divided into income quartiles according to their highest annual income during 2004-2018 and into three categories based on educational attainment. The outcome was the first redeemed OAC prescription.Results: We identified 239 222 patients (mean age 72.7 ± 13.2 years, 49.8% female) with incident AF during 2007-2018. Higher income was associated with higher OAC initiation rate: compared to the lowest income quartile the adjusted SHRs (95% CI) for OAC initiation were 1.09 (1.07-1.10), 1.13 (1.11-1.14) and 1.13 (1.12-1.15) in the second, third and fourth income quartiles, respectively. Patients in the highest educational category had a slightly lower OAC initiation rate than patients in the lowest educational category (adjusted SHR 0.92 [95% CI 0.90-0.93]). Income-related disparities were larger and education-related disparities only marginal among patients at high risk of ischemic stroke. The socioeconomic disparities in OAC initiation within 1-year follow-up decreased from 2007 to 2018. The adoption of direct OACs as the initial anticoagulant was faster among patients with higher income or educational levels.Conclusion: These findings highlight potential missed opportunities in stroke prevention, especially among AF patients with low income, whereas the education-related disparities in OAC initiation appear controversial.</p