Protein molecular weight computation from sedimentation velocity data

In ultracentrifugation, the concentration gradient of mono-disperse samples obtained by sedimentation velocity experiments is described by Gehatia's equation which holds several parameters including the sedimentation and diffusion constants. Once these two constants are known, the molecular weight follows from the Svedberg equation. A least squares method has been developed to derive the transport constants from the refractive index gradient curves. The method employs a mathematical model based on Gehatia's theory. A main feature of the model is the application of two sets of intermediate parameters via which the transport coefficients are much casier calculated than along a direct way. Furthermore some difficult to observe quantities cancel out. The square residues are minimised numerically. The potential errors introduced by this numerical minimalisation are shown to be unimportant compared to the unavoidable experimental errors

Antioxidants and air pollution in relation to indicators of asthma and COPD

Two main research questions were specified in this thesis. First, whether acute respiratory effects of air pollution can be modulated by antioxidants. Second, whether dietary or plasma antioxidants were associated with indicators of asthma and COPD.Two intervention studies investigated a possible modulation of the acute respiratory effects of ozone by antioxidant supplementation. In addition a panel study examined a possible modulation of the acute respiratory effects of winter air pollution by antioxidants in diet and serum.The first intervention study in 1994 was a pilot study among 26 cyclists who performed lung function measurements (192 observations) before and after exercise. Half of the group was randomly assigned to the supplementation group and were given a daily antioxidant supplementation of vitamins C, E andβ-carotene. The control group did not receive a placebo. We repeated the study in the summer of 1996 with a similar design but this time the study was placebo-controlled. In this study, 38 subjects (380 lung function measurements) participated until the end of the study and the antioxidant supplementation consisted of a cocktail of vitamins C and E.Both intervention studies suggest that there was an effect of ozone on FEV 1 and FVC in the control group. There was no change in lung function when ozone levels were high in the supplementation group. The difference in ozone effect between the groups for both studies was statistically significant for FEV 1 and FVC. In the analysis of the panel study, we included only subjects with chronic respiratory symptoms because these subjects showed clear acute respiratory effects of air pollution. The results suggest that subjects with low levels of plasmaβ-carotene showed an effect of air pollution on large PEF decrements, in particular, for PM10 and black smoke, whereas subjects with high levels of plasmaβ-carotene did not show an effect of air pollution. No difference in acute respiratory effects of air pollution was observed for a high versus a low dietary intake of vitamin C, E andβ-carotene or for plasmaα-tocopherol.The second research question was investigated within the MORGEN study. This study is a cross-sectional investigation on the prevalence of risk factors for chronic diseases using self-administered questionnaires and a physical examination in a randomly selected sample of the Dutch population.First, we examined the relations between dietary antioxidants (vitamins C, E andβ-carotene) and the prevalence of a number of respiratory symptoms and lung function in a population based sample of 6,555 adults. Our results suggested that a high dietary vitamin C andβ-carotene intake was associated with a higher FEV 1 and FVC. Dietary vitamin E was not associated with lung function. None of the dietary antioxidants were consistently associated with the prevalence of a number of respiratory symptoms.Second, we studied the relation between plasma levels ofβ-carotene orα-tocopherol and respiratory symptoms in a case-control sample of never and long-term former smokers. Our results suggested that cases (subjects with one or more chronic respiratory symptoms; n=491) tended to have lower plasmaβ-carotene levels than controls (n=496). Plasmaα-tocopherol was not associated with asthma and chronic bronchitis symptoms but was positively associated with dyspnea. This adverse association of plasmaα-tocopherol could not be explained by adjustment for cardiovascular risk factors and remains puzzling. Third, we evaluated the relation between plasma antioxidants (β-carotene andα-tocopherol) and lung function in a random sample (n=367) of the MORGEN study. We found that subjects with a high plasmaβ-carotene concentration tended to have a higher FVC and FEV 1 than subjects with a low plasmaβ-carotene concentration but this was not statistically significant for FEV 1 . Plasmaα-tocopherol was not associated with lung function.</p

Immunity in atherosclerosis: novel assays, biomarkers and therapeutic approaches

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology. Additional treatment could be achieved via immunomodulation. We aimed to identify potential biomarkers for monitoring of immunomodulatory drugs in future clinical trials and investigated pharmacological modulation of atherogenic pathways. We identified smokers and elderly healthy people as suitable groups for future clinical trials. We investigated the impact of sample aging on LPS responses, and optimized methodology for evaluation of LPS-driven neutrophil responses, in vitro and in vivo. As potential anti-atherogenic strategy, we evaluated the effect of pneumococcal vaccination on circulating oxLDL-IgM levels in man. The immunomodulatory impact of hydroxychloroquine, a drug with potential anti-atherogenic effects, was evaluated in healthy volunteers. A novel OX40L inhibitor was tested in healthy volunteers, since the OX40-OX40L axis may play a role in atherogenesis. OX40L inhibition was safe and effectively reduced T cell activity. Lastly, we showed that PD-1 agonism reduced atherosclerosis in Ldlr-/- mice. This thesis adds to the future development of effective and specific immunomodulatory treatments for atherosclerosis.Drug Delivery Technolog

Symptom attribution and presentation in general practice after an extreme life event

Background. A serious life event is likely to shape attributions relating to symptoms experienced afterwards. While they may play an important role in prognosis and seeking care, such perceptions have hardly been studied among survivors of a disaster. Objective. To investigate the association between self-reported health problems that have been attributed to an extreme life event and the symptoms presented to GPs. Methods. A two-wave longitudinal survey (2–3 weeks and 18 months) among survivors of a fireworks disaster was combined with a continuous morbidity surveillance in general practice. Symptoms attributed to the disaster reported in an open-ended question in the two waves were analysed using descriptive statistics. Differences in presented symptoms over time were analysed using logistic multilevel analysis. Results. More than half of the respondents reported health problems, which were, in their opinion, related to the disaster. Psychological problems were most frequently reported in association with the disaster, and in contrast to physical attributed symptoms, presentation of these problems in general practice decreased over time. In the total sample, musculoskeletal symptoms were less frequently presented in the longer term. Survivors who attributed symptoms to the disaster at both waves or after 18 months only most often presented such symptoms to the GP. Conclusion. Survivors attributed psychological problems and physical symptoms to the disaster at short-term and midterm post-disaster. Most of these survivors presented such symptoms to the GP. Attribution of symptoms to an extreme life event such as a disaster may therefore require special attention from the GP. (aut. ref

Health-related quality of life and mental health problems after a disaster: Are chronically ill survivors more vulnerable to health problems?

Studies have shown that the chronically ill are at higher risk for reduced health-related quality of life (HRQL) and for mental health problems. A combination with traumatic events might increase this risk. This longitudinal study among 1216 survivors of a disaster examines whether chronically ill survivors had a different course of HRQL and mental health problems compared to survivors without chronic diseases. HRQL and mental health problems were measured 3 weeks, 18 months and 4 years post-disaster. Data on pre-disaster chronic diseases was obtained from the electronic medical records of general practitioners. Random coefficient analyses showed significant interaction effects for social functioning, bodily pain and emotional role limitations at T2 only. Chronically ill survivors did not consistently have a different course of general health, physical role limitations, and mental health problems. In conclusion, chronic diseases were not an important risk factor for impaired HRQL and mental health problems among survivors

The Public Health Dimension of Disasters—Health Outcome Assessment of Disasters

A broad range of health problems are related to disasters. Insight into these health problems is needed for targeted disaster management. Disaster health outcome assessment can provide insight into the health effects of disasters. During the 15th World Congress on Disaster and Emergency Medicine in Amsterdam (2007), experts in the field of disaster epidemiology discussed important aspects of disaster health outcome assessment, such as: (1) what is meant by disaster health outcome assessment?; (2) why should one conduct a disaster health outcome assessment, and what are the objectives?, and (3) who benefits from the information obtained by a disaster health outcome assessment? A disaster health outcome assessment can be defined as a systematic assessment of the current and potential health problems in a population affected by a disaster. Different methods can be used to examine these health problems such as: (1) rapid assessment of health needs; (2) (longitudinal) epidemiological studies using questionnaires; (3) continuous surveillance of health problems using existing registration systems; (4) assessment of the use and distribution of health services; and (5) research into the etiology of the health effects of disasters. The public health impact of a disaster may not be immediately evident. Disaster health outcome assessment provides insight into the health related consequences of disasters. The information that is obtained by performing a disaster health outcome assessment can be used to initiate and adapt the provision of health care. Besides information for policy-makers, disaster health outcome assessments can contribute to the knowledge and evidence base of disaster health outcomes (scientific objective). Finally, disaster health outcome assessment might serve as a signal of recognition of the problems of the survivors. Several stakeholders may benefit from the information obtained from a disaster health outcome assessment. Disaster decision-makers and the public health community benefit from performing a disaster health outcome assessment, since it provides information that is useful for the different aspects of disaster management. Also, by providing information about the nature, prevalence, and course of health problems, (mental) health care workers can anticipate the health needs and requirements in the affected population. It is important to realize that the disaster is not over when the acute care has been provided. Instead, disasters will cause many other health problems and concerns such as infectious diseases and mental health problems. Disaster health outcome assessments provide insight into the public health impact of disaster

Impact of oral administration of single strain Lactococcus lactis spp. cremoris on immune responses to keyhole limpet hemocyanin immunization and gut microbiota: A randomized placebo-controlled trial in healthy volunteers

IntroductionLactococcus lactis spp. cremoris has been associated with promising immunomodulatory results in preclinical trials. The aim of this study was to investigate the pharmacodynamic (PD) effects of three monoclonal microbial formulations of L. lactis spp. cremoris (EDP1066) on the immune response to keyhole limpet hemocyanin (KLH). Potential effects on the gut microbiota were also investigated.MethodsThe trial was registered on Netherlands Trial Register (trial ID NL7519, https://trialsearch.who.int). Eighty-one healthy subjects (median 28, range 18–59 years) were randomized to 28 days of enteric-coated capsules at five doses (n = 13) (1.5 * 1012 total cells daily), freeze-dried powder at one dose (n = 12) (3.0 * 1011 total cells daily) or five doses (n = 12), minitablets at one dose (n = 12) or five doses (n = 12), or placebo (n = 20) prior to KLH immunization. Antibody responses and circulating regulatory T cells (Tregs) were measured after KLH immunization, and skin responses were evaluated after a KLH rechallenge by laser speckle contrast imaging and multispectral imaging. Ex vivo lymphocyte (phytohemagglutinin) and monocyte (lipopolysaccharide (LPS)) cytokine release assays were explored in the minitablet-treated groups only. The prevalence of L. lactis spp. cremoris in the gastrointestinal tract and the impact on the fecal microbiota were assessed by qPCR and 16S rRNA sequencing, respectively.ResultsRepeated-measures analysis of covariances revealed no significant treatment effects on the antibody responses to KLH, number of Tregs, or KLH skin rechallenge outcomes. Ex vivo LPS-driven cytokine responses in whole blood were lower in the low dose minitablet group compared to placebo: tumor necrosis factor (estimated difference (ED) from placebo: −44.2%, 95% confidence interval (CI) −65.3% to −10.3%), interleukin (IL)-1β (ED −41.4%, 95% CI −63.5% to −5.8%), and IL-6 (ED −39.2%, 95% CI −56.8% to −14.5%). The fecal presence of L. lactis spp. cremoris increased during treatment by all EDP1066 formulations and normalized 5 days after the last dose. Microbiome α-diversity did not change by the treatments compared to placebo.DiscussionThe EDP1066 formulations did not affect the immune response to KLH immunization in healthy individuals. However, exposure to L. lactis spp. cremoris in minitablet formulation impacted ex vivo whole blood LPS cytokine response. The clinical impact of these effects awaits further investigations.Netherlands Trial Registertrialsearch.who.int, trial ID NL7519

Challenges and opportunities for process intensification in Europe from a process systems engineering perspective

Process Intensification (PI) is an effective way to enhance process efficiency and sustainability at affordable costs and efforts, attracting particular interest in the European area, as one of the most important chemical production areas in the world. PI primarily contributes by developing and testing new processing technologies that once integrated within a process improve the overall process performance substantially but as a result, it may alter the overall process (flowsheet) structure and its dynamic behavior. As such PI plays a key role in improving energy efficiency, optimizing resource allocation, and reducing environmental impact of industrial processes, and thereby leading to a cost-effective, eco-efficient, low-carbon and sustainable industry. However, along with opportunities, the PI new technologies have challenges related to failures in longer-term performance. In this respect, Process Systems Engineering (PSE) stance is more on integration aspects of new PI technologies into processes by making process (re)designs, doing operability studies, and performance optimizations within a supply chain setting. PSE contributes to overcoming the challenges by providing systematic approaches for the design and optimization of PI technologies. This perspective paper is a lightly referenced scholarly opinion piece about the status and directions of process intensification field from a PSE viewpoint. Primarily, it focuses on PSE perspectives towards sustainable lower energy usage process systems and provides a brief overview of the current situation in Europe. It also emphasizes the key challenges and opportunities for (new) PI technologies considering their integration in a process in terms of process synthesis and design, process flowsheet optimization, process and plantwide control, (green) electrification, sustainability improvements. Potential research directions on these aspects are given from an industrial and academic perspective of the authors