Single-Walled Carbon Nanotubes as Shadow Masks for Nanogap Fabrication

We describe a technique for fabricating nanometer-scale gaps in Pt wires on insulating substrates, using individual single-walled carbon nanotubes as shadow masks during metal deposition. More than 80% of the devices display current-voltage dependencies characteristic of direct electron tunneling. Fits to the current-voltage data yield gap widths in the 0.8-2.3 nm range for these devices, dimensions that are well suited for single-molecule transport measurements

Spin dependent transport of ``nonmagnetic metal/zigzag nanotube encapsulating magnetic atoms/nonmagnetic metal'' junctions

Towards a novel magnetoresistance (MR) device with a carbon nanotube, we propose ``nonmagnetic metal/zigzag nanotube encapsulating magnetic atoms/nonmagnetic metal'' junctions. We theoretically investigate how spin-polarized edges of the nanotube and the encapsulated magnetic atoms influence on transport. When the on-site Coulomb energy divided by the magnitude of transfer integral, $U/|t|$, is larger than 0.8, large MR effect due to the direction of spins of magnetic atoms, which has the magnitude of the MR ratio of about 100%, appears reflecting such spin-polarized edges.Comment: 4 pages, 3 figures, accepted for publication in Synth. Metal

Socioeconomic differences in working life expectancy:a scoping review

Background: In the last decade, interest in working life expectancy (WLE) and socioeconomic differences in WLE has grown considerably. However, a comprehensive overview of the socioeconomic differences in WLE is lacking. The aim of this review is to systematically map the research literature to improve the insight on differences in WLE and healthy WLE (HWLE) by education, occupational class and income while using different ways of measuring and estimating WLE and to define future research needs. Methods: A systematic search was carried out in Web of Science, PubMed and EMBASE and complemented by relevant publications derived through screening of reference lists of the identified publications and expert knowledge. Reports on differences in WLE or HWLE by education, occupational class or income, published until November 2022, were included. Information on socioeconomic differences in WLE and HWLE was synthesized in absolute and relative terms. Results: A total of 26 reports from 21 studies on educational and occupational class differences in WLE or HWLE were included. No reports on income differences were found. On average, WLE in persons with low education is 30% (men) and 27% (women) shorter than in those with high education. The corresponding numbers for occupational class difference were 21% (men) and 27% (women). Low-educated persons were expected to lose more working years due to unemployment and disability retirement than high-educated persons. Conclusions: The identified socioeconomic inequalities are highly relevant for policy makers and pose serious challenges for equitable pension policies. Many policy interventions aimed at increasing the length of working life follow a one-size-fits-all approach which does not take these inequalities into account. More research is needed on socioeconomic differences in HWLE and potential influences of income on working life duration.</p

Single-molecule transistor fabrication by self-aligned lithography and in situ molecular assembly

Abstract We describe the fabrication of single-molecule transistors by self-aligned lithography and in situ molecular assembly. Ultrathin metallic electrodes are patterned with a nanoscale interelectrode separation defined by the lateral oxidation of a thin layer of Al. Highly conjugated molecular units are sequentially assembled within the electrode gap by selective design of the molecular end group chemistry. The assembled devices display evidence of molecular conduction

Interleukin-2 PET imaging in patients with metastatic melanoma before and during immune checkpoint inhibitor therapy

PURPOSE: Immune checkpoint inhibitors can induce a T cell-mediated anti-tumor immune response in patients with melanoma. Visualizing T cell activity using positron emission tomography (PET) might allow early insight into treatment efficacy. Activated tumor-infiltrating T cells express the high-affinity interleukin-2 receptor (IL-2R). Therefore, we performed a pilot study, using fluorine-18-labeled IL-2 ([18F]FB-IL2 PET), to evaluate whether a treatment-induced immune response can be detected. METHODS: Patients with metastatic melanoma received ~ 200 MBq [18F]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [18F]FB-IL2 uptake was measured as standardized uptake value in healthy tissues (SUVmean) and tumor lesions (SUVmax). Response to therapy was assessed using RECIST v1.1. Archival tumor tissues were used for immunohistochemical analyses of T cell infiltration. RESULTS: Baseline [18F]FB-IL2 PET scans were performed in 13 patients. SUVmean at baseline was highest in the kidneys (14.2, IQR: 11.6-18.0) and liver (10.6, IQR: 8.6-13.4). In lymphoid tissues, uptake was highest in spleen (10.9, IQR: 8.8-12.4) and bone marrow (2.5, IQR: 2.1-3.0). SUVmax in tumor lesions (n = 41) at baseline was 1.9 (IQR: 1.7-2.3). In 11 patients, serial imaging was performed, three at week 6, seven at week 2, and one at week 4. Median [18F]FB-IL2 tumor uptake decreased from 1.8 (IQR: 1.7-2.1) at baseline to 1.7 (IQR: 1.4-2.1) during treatment (p = 0.043). Changes in [18F]FB-IL2 tumor uptake did not correlate with response. IL-2R expression in four archival tumor tissues was low and did not correlate with baseline [18F]FB-IL2 uptake. No [18F]FB-IL2-related side effects occurred. CONCLUSION: PET imaging of the IL-2R, using [18F]FB-IL2, is safe and feasible. In this small patient group, serial [18F]FB-IL2-PET imaging did not detect a treatment-related immune response. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02922283; EudraCT: 2014-003387.20

Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy

Response evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of the tumor and opportunities to evaluate tumor response during therapy. Quantification of tumor-specific mutations in plasma correlates well with tumor burden. Moreover, with liquid biopsies, it is also possible to detect mutations causing secondary resistance during treatment. This review focuses on the clinical utility of ctDNA as a response and follow-up marker in patients with non-small cell lung cancer, melanoma, colorectal cancer, and breast cancer. Relevant studies were retrieved from a literature search using PubMed database. An overview of the available literature is provided and the relevance of ctDNA as a response marker in anti-cancer therapy for clinical practice is discussed. We conclude that the use of plasma-derived ctDNA is a promising tool for treatment decision-making based on predictive testing, detection of resistance mechanisms, and monitoring tumor response. Necessary steps for translation to daily practice and future perspectives are discussed

The course of traumatic pancreatitis in a patient with pancreas divisum: a case report

BACKGROUND: The peculiar anatomy of pancreatic ducts in pancreas divisum (PD) may interfere with the development of acute chronic pancreatitis. In the presented case, PD influenced the evolution of lesions after pancreatic trauma. CASE PRESENTATION: A 38 years old patient refferred to our hospital with recurrent episodes of mild pancreatitis during the last two years. The first episode occurred four months after blunt abdominal trauma. Endoscopic Retrograde Cholangiopancreatography, Magnetic Resonance Imaging of upper abdomen and Magnetic Resonance Cholangiopancreatography disclosed pancreas divisum, changes consistent with chronic pancreatitis in the dorsal pancreatic duct, atrophy in the body and tail of the pancreas and a pseudocyst in the pancreatic head, that was drained endoscopically. CONCLUSION: Pancreas Divisum may interfere with the evolution of posttraumatic changes in the pancreas after blunt abdominal trauma

Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome

Purpose: Variants in the DNA mismatch repair (MMR) gene MSH6, identified in individuals suspected of Lynch syndrome, are difficult to classify owing to the low cancer penetrance of defects in that gene. This not only obfuscates personalized health care but also the development of a rapid and reliable classification procedure that does not require clinical data. Methods: The complete in vitro MMR activity (CIMRA) assay was calibrated against clinically classified MSH6 variants and, employing Bayes’ rule, integrated with computational predictions of pathogenicity. To enable the validation of this two-component classification procedure we have employed a genetic screen to generate a large set of inactivating Msh6 variants, as proxies for pathogenic variants. Results: The genetic screen-derived variants established that the two-component classification procedure displays high sensitivities and specificities. Moreover, these inactivating variants enabled the direct reclassification of human variants of uncertain significance (VUS) as (likely) pathogenic. Conclusion: The two-component classification procedure and the genetic screens provide complementary approaches to rapidly and cost-effectively classify the large majority of human MSH6 variants. The approach followed here provides a template for the classification of variants in other disease-predisposing genes, facilitating the translation of personalized genomics into personalized health care