Probing the charge of a quantum dot with a nanomechanical resonator

We have used the mechanical motion of a carbon nanotube (CNT) as a probe of the average charge on a quantum dot. Variations of the resonance frequency and the quality factor are determined by the change in average charge on the quantum dot during a mechanical oscillation. The average charge, in turn, is influenced by the gate voltage, the bias voltage, and the tunnel rates of the barriers to the leads. At bias voltages that exceed the broadening due to tunnel coupling, the resonance frequency and quality factor show a double dip as a function of gate voltage. We find that increasing the current flowing through the CNT at the Coulomb peak does not increase the damping, but in fact decreases damping. Using a model with energy-dependent tunnel rates, we obtain quantitative agreement between the experimental observations and the model. We theoretically compare different contributions to the single-electron induced nonlinearity, and show that only one term is significant for both the Duffing parameter and the mode coupling parameter. We also present additional measurements which support the model we develop: Tuning the tunnel barriers of the quantum dot to the leads gives a 200-fold decrease of the quality factor. Single-electron tunneling through an excited state of the CNT quantum dot also changes the average charge on the quantum dot, bringing about a decrease in the resonance frequency. In the Fabry-P\'{e}rot regime, the absence of charge quantization results in a spring behaviour without resonance frequency dips, which could be used, for example, to probe the transition from quantized to continuous charge with a nanomechanical resonator.Comment: 17 pages, 12 figure

Skin autofluorescence is increased in patients with carotid artery stenosis and peripheral artery disease

Advanced glycation end products (AGEs) have a pivotal role in atherosclerosis. We evaluated skin autofluorescence (SAF), a non-invasive measurement of tissue AGE accumulation, in patients with carotid artery stenosis with and without coexisting peripheral artery occlusive disease (PAOD). SAF was measured using the AGE Reader™ in 56 patients with carotid artery stenosis and in 56 age- and sex-matched healthy controls without diabetes, renal dysfunction or known atherosclerotic disease. SAF was higher in patients with carotid artery stenosis compared to the control group: mean 2.81 versus 2.46 (P = 0.002), but especially in the younger age group of 50–60 years old: mean 2.82 versus 1.94 (P = 0.000). Patients with carotid artery stenosis and PAOD proved to have an even higher SAF than patients with carotid artery stenosis only: mean 3.28 versus 2.66 (P = 0.003). Backward linear regression analysis showed that age, smoking, diabetes mellitus, renal function and the presence of PAOD were the determinants of SAF, but carotid artery stenosis was not. SAF is increased in patients with carotid artery stenosis and PAOD. The univariate and multivariate associations of SAF with age, smoking, diabetes, renal insufficiency and PAOD suggest that increased SAF can be seen as an indicator of widespread atherosclerosis

Post-irradiation diarrhea : (a study of its mechanism after pelvic irradiation)

In radiotherapy of pelvic cancers, the X-ray dose to be delivered to the tumour is limited by the tolerance of healthy surrounding tissue. In the past, with orthovoltage equipment, skin tolerance was the main limiting factor. With the introduction of megavoltage equipment, it became possible to deliver a higher radiation dose to deep-seated lesions, but inevitably also to neighbouring normal tissues. As a result, local cure rates were increased, but so was the number of complications. In recent years we encountered a number of serious complications of irradiation of pelvic organs. It was in particular in cases of ovarian cancer where a higher dose of irradiation was applied that these distressing complications were frequent. This experience led to a more conservative irradiation protocol in these cases, resulting in a marked fall in the number of complications. In cervical and endometrial cancer the damage never was as extensive as in the ovarian cancer group. At present many patients who have to ondergo pelvic irradiation, however, will have transient or longer lasting symptoms caused by the irradiation. Modern radiotherapy necessitates the acceptance of a calculated risk of complications in order to achieve a better cure rate. To calculate these risks, one has to know the radiation dose-effect relationship of normal tissues. In quantitative terms these risks are insufficiently known. The normal tissues most at risk when treating pelvic tumours are the bladder, the ureters, the rectum, the sigmoid colon and the small intestine. In this study we limit ourselves to the bowel. The literature regarding postirradiation bowel complications is very confusing. In the first place no two authors used the same criteria for what they consider to be bowel complications. Some authors only include severe complications like stenoses of the bowel and fistulas, in particular those that require surgical intervention (5, 8). Other authors include patients with diarrhea and/ or malabsorption, whereas a third group will include ill defined situations that necessitate long-term hospitalization. It is clear that in this way severe and mild complications are often mixed. The result is that in different series the incidence of severe gastro-intestinal complications varies as much as from I to 15"7o (l-12).lt is to be noted that in these studies damage to the small intestine form only a minority. Another drawback of the reported studies is that all were retrospective. In addition when patients appear to have a recurrence of their tumour in parallel with radiation damage, they are often excluded from further evaluation. In view of the rarity of the severe postirradiation bowel syndromes, a prospective study of these complications would require a very large number of patients. This type of study has never been undertaken

Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is not related to the number of pregnancies

Highlights Skin autofluorescence (SAF) assesses subcutaneous accumulation of advanced glycation end products and has been shown to predict future cardiovascular disease and diabetes. A higher number of pregnancies was significantly associated with higher SAF, even after correction for relevant confounders like waist circumference, creatinine clearance, and diabetes status, but not after correction for age. Women with the highest SAF Z-score had a more unfavorable risk factor profile, with higher body mass index and waist circumference, higher blood pressure, lower high-density lipoprotein cholesterol, and higher triglyceride levels

Is skin autofluorescence (SAF) representative of dermal advanced glycation endproducts (AGEs) in dark skin?:A pilot study

Aims: Non-invasively assessed skin autofluorescence (SAF) measures advanced glycation endproducts (AGEs) in the dermis. SAF correlates with dermal AGEs in Caucasians and Asians, but studies in dark-skinned subjects are lacking. In this pilot we aimed to assess whether SAF signal is representative of intrinsic fluorescence (IF) and AGE accumulation in dark skin. Methods: Skin biopsies were obtained in 12 dark-skinned subjects (6 healthy subjects, median age 22 years; 6 diabetes mellitus (DM) subjects, 65 years). SAF was measured with the AGE Reader, IF using confocal microscopy, and AGE distribution with specific antibodies. CML and MG-H1 were quantified with UPLC-MS/MS and pentosidine with HPLC and fluorescent detection. Results: SAF correlated with IF from the dermis (405nm, r = 0.58, p < 0.05), but not with CML (r = 0.54, p = 0.07). CML correlated with IF from the dermis (405nm, r = 0.90, p < 0.01). UV reflectance and the coefficient of variation of SAF were negatively correlated (r = -0.80, p < 0.01). CML and MG-H1 were predominantly present around blood vessels, in collagen and fibroblasts in the dermis. Conclusion: This proof of concept study is the first to compare non-invasive SAF with AGE levels measured in skin biopsies in dark-skinned subjects. SAF did not correlate with individual AGEs from biopsies, but was associated with IF. However, the intra-individual variance was high, limiting its application in dark-skinned subjects on an individual basis

From pixels to pathophysiology - imaging immunity in cerebro- and cardiovascular disease

This thesis, consisting of six experimental chapters, shows the advantages of using high-field MRI and PET imaging together with targeted contrast agents and tracers for understanding pathophysiology and monitoring disease progression. We employed various translational imaging techniques in experimental animal models to elucidate the functioning of the immune system in cerebro- and cardiovascular diseases, predominantly focusing on ischemic stroke and myocardial infarction. The first part focuses on multimodal imaging of immune processes after acute, subacute and chronic myocardial infarction and stroke. The second part focuses on proof-of-concept studies with a novel radiotracer and a nanoparticle platform which can be applied for theranostic (i.e. therapeutic and diagnostic) purposes. For the second part, well-established disease models for ischemic heart disease, atherosclerosis and heart allograft transplantation were applied to demonstrate the efficiency of the radiotracer and the nanobiologic platform. The experiments detailed in this thesis represent a modest step forward in identifying imaging methods and targets of interest for understanding pathophysiology of stroke and myocardial infarction. Examples, such as evaluating the metabolic activity of a stroke lesion, mapping myeloid cell trafficking after an ischemic event, or assessing vascular integrity of the bone marrow, showcase the potential for imaging biomarkers. While individually these biomarkers may not bring in drastic changes in treatment paradigms, their true potential lies in integration. When combined with acute treatment, laboratory tests, functional assessments, and immunomodulatory interventions, these imaging biomarkers may consolidate into a comprehensive and individually relevant tool for guiding treatment decisions and influencing recovery strategies

Accumulation of advanced glycation end (AGEs) products in intensive care patients: an observational, prospective study

<p>Abstract</p> <p>Background</p> <p>Oxidative stress plays an important role in the course and eventual outcome in a majority of patients admitted to the intensive care unit (ICU). Markers to estimate oxidative stress are not readily available in a clinical setting. AGEs accumulation has been merely described in chronic conditions, but can also occur acutely due to oxidative stress. Since AGEs have emerged to be stable end products, these can be a marker of oxidative stress. Skin autofluorescence (AF) is a validated marker of tissue content of AGEs. We hypothesized that AGEs accumulate acutely in ICU patients.</p> <p>Methods</p> <p>We performed an observational prospective study in a medical surgical ICU in a university affiliated teaching hospital. All consecutively admitted ICU patients in a 2 month period were included. Skin AF was measured using an AGE reader in 35 consecutive ICU patients > 18 yrs. As a comparison, historical data of a control group (n = 231) were used. These were also used to calculate age-adjusted AF-levels (AF_adj). Values are expressed as median and interquartile range [P₂₅-P₇₅]. Differences between groups were tested by non parametric tests. P < 0.05 was considered statistically significant.</p> <p>Results</p> <p>AF_adjvalues were higher in ICU patients (0.33 [0.00 - 0.68]) than in controls (-0.07 [-0.29 - 0.24]; P < 0.001). No differences in skin AF_adjwere observed between acute or planned admissions, or presence of sepsis, nor was skin AF_adjrelated to severity of disease as estimated by APACHE-II score, length of ICU, hospital stay or mortality.</p> <p>Conclusion</p> <p>Acute AGE accumulation in ICU patients was shown in this study, although group size was small. This can possibly reflect oxidative stress in ICU patients. Further studies should reveal whether AGE-accumulation will be a useful parameter in ICU patients and whether skin AF has a predictive value for outcome, which was not shown in this small study.</p