Noise Thermometry with Two Weakly Coupled Bose-Einstein Condensates

Here we report on the experimental investigation of thermally induced fluctuations of the relative phase between two Bose-Einstein condensates which are coupled via tunneling. The experimental control over the coupling strength and the temperature of the thermal background allows for the quantitative analysis of the phase fluctuations. Furthermore, we demonstrate the application of these measurements for thermometry in a regime where standard methods fail. With this we confirm that the heat capacity of an ideal Bose gas deviates from that of a classical gas as predicted by the third law of thermodynamics.Comment: 4 pages, 4 figure

Proof for trivalent Sc ions in Sc2@C84 from high-energy spectroscopy

The electronic structure and the valency of the Sc ions in the endohedral dimetallofullerene Sc 2 @C 84 with D 2d symmetry are probed using high-energy spectroscopy. Comparison of the Sc 2p ! 3d x-ray-absorption spectrum with calculated ionic multiplet spectra shows that the Sc ions are trivalent. Detailed multiplet calcu-lations including covalency indicate that the effective valency of the Sc~III! ions can be described by a formal charge transfer to the fullerene cage of 2.660.1. This illustrates that a purely ionic picture is not valid for the electronic structure of Sc 2 @C 84 , and that a more complex picture including finite hybridization between the Sc and the fullerene cage has to be applied

Reconsider radiation exposure from imaging during immune checkpoint inhibitor trials to reduce risk of secondary cancers in long-term survivors?

Immune checkpoint inhibitors (ICI) have improved outcomes for patients with advanced cancers, and results in increasing numbers of long-term survivors. For registration studies, progression-free survival and disease-free survival often serve as primary endpoints. This requires repeated computed tomography (CT) scans for tumour imaging which might lead to major radiation exposure. To determine this, all immune checkpoint inhibitors trials that led to FDA approval were retrieved up to July 29, 2019. From the available protocols, imaging modalities and schedules used in each trial were identified. The anticipated cumulative number of scans made after 1, 3, 5, and 10 years study participation were calculated. The percentage of lifetime attributable cancer risk was calculated using the Biological Effects of Ionizing Radiation VII report. Fifty-one trials were identified, from which 39 protocols were retrieved. Four were adjuvant trials. All protocols required repeated chest-abdomen imaging and specified CT scans as preferred imaging modality. Median calculated cumulative numbers of chest-abdomen CT scans after 1, 3, 5, and 10 years study participation were 7, 16, 24 and 46, respectively. For ages 20-70 years at study entry, the average lifetime attributable cancer risk after 1 year of study participation ranged from 1.11 to 0.40% for men and from 1.87 to 0.46% for women. At 10 years study participation, this risk increased to a range of 5.91 to 1.96% for men and 9.64 to 2.32% for women. Given high imaging radiation exposure for long-term survivors in current ICI trials an adaptive imaging interval and imaging termination rules should be considered for long-term survivors

Generalised-Lorentzian Thermodynamics

We extend the recently developed non-gaussian thermodynamic formalism \cite{tre98} of a (presumably strongly turbulent) non-Markovian medium to its most general form that allows for the formulation of a consistent thermodynamic theory. All thermodynamic functions, including the definition of the temperature, are shown to be meaningful. The thermodynamic potential from which all relevant physical information in equilibrium can be extracted, is defined consistently. The most important findings are the following two: (1) The temperature is defined exactly in the same way as in classical statistical mechanics as the derivative of the energy with respect to the entropy at constant volume. (2) Observables are defined in the same way as in Boltzmannian statistics as the linear averages of the new equilibrium distribution function. This lets us conclude that the new state is a real thermodynamic equilibrium in systems capable of strong turbulence with the new distribution function replacing the Boltzmann distribution in such systems. We discuss the ideal gas, find the equation of state, and derive the specific heat and adiabatic exponent for such a gas. We also derive the new Gibbsian distribution of states. Finally we discuss the physical reasons for the development of such states and the observable properties of the new distribution function.Comment: 13 pages, 1 figur

Molecular imaging biomarkers for immune checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICIs) have substantially changed the field of oncology over the past few years. ICIs offer an alternative treatment strategy by exploiting the patients’ immune system, resulting in a T cell mediated anti-tumor response. These therapies are effective in multiple different tumor types. Unfortunately, a substantial group of patients do not respond to ICIs. Molecular imaging, using single-photon emission computed tomography (SPECT) and positron emission tomography (PET), can provide non-invasive whole-body visualization of tumor and immune cell characteristics and might support patient selection or response evaluations for ICI therapies. In this review, recent studies with 18F-fluorodeoxyglucose-PET imaging, imaging of immune checkpoints and imaging of immune cells will be discussed. These studies are until now mainly exploratory, but the first results suggest that molecular imaging biomarkers could have a role in the evaluation of ICI therapy

Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types

The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allows prediction of biologically relevant overexpression of proteins from a robust data set of mRNA microarrays. This technique was used in a database comprising 19,746 tumors to identify for 41 tumor types the percentage of samples with an overexpression of MSLN compared to a normal background. A literature search was performed to compare the FGM profiling data with studies reporting IHC MSLN tumor expression. FGM profiling showed MSLN overexpression in gastrointestinal (12-36%) and gynecological tumors (20-66%), non-small cell lung cancer (21%) and synovial sarcomas (30%). The overexpression found in thyroid cancers (5%) and renal cell cancers (10%) was not yet reported with IHC analyses. We observed that MSLN amplification rate within esophageal cancer depends on the histotype (31% for adenocarcinomas versus 3% for squamous-cell carcinomas). Subset analysis in breast cancer showed MSLN amplification rates of 28% in triple-negative breast cancer (TNBC) and 33% in basal-like breast cancer. Further subtype analysis of TNBCs showed the highest amplification rate (42%) in the basal-like 1 subtype and the lowest amplification rate (9%) in the luminal androgen receptor subtype

Aziz Nesin:Acelem var

Taha Toros Arşivi, Dosya No: 56-Aziz Nesi

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

Functional Genomic mRNA Profiling of Colorectal Adenomas:Identification and in vivo Validation of CD44 and Splice Variant CD44v6 as Molecular Imaging Targets

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. High adenoma miss rates, especially seen in high-risk patients, demand for better endoscopic detection. By fluorescently \u27highlighting\u27 specific molecular characteristics, endoscopic molecular imaging has great potential to fulfill this need. To implement this technique effectively, target proteins that distinguish adenomas from normal tissue must be identified. In this study we applied in silico Functional Genomic mRNA (FGmRNA) profiling, which is a recently developed method that results in an enhanced view on the downstream effects of genomic alterations occurring in adenomas on gene expression levels. FGmRNA profiles of sporadic adenomas were compared to normal colon tissue to identify overexpressed genes. We validated the protein expression of the top identified genes, AXIN2, CEMIP, CD44 and JUN, in sporadic adenoma patient samples via immunohistochemistry (IHC). CD44 was identified as the most attractive target protein for imaging purposes and we proved its relevance in high-risk patients by demonstrating CD44 protein overexpression in Lynch lesions. Subsequently, we show that the epithelial splice variant CD44V6 is highly overexpressed in our patient samples and we demonstrated the feasibility of visualizing adenomas in ApcMin/+ mice in vivo by using a fluorescently labeled CD44v6 targeting peptide. In conclusion, via in silico functional genomics and ex vivo protein validation, this study identified CD44 as an attractive molecular target for both sporadic and high-risk Lynch adenomas, and demonstrates the in vivo applicability of a small peptide drug directed against splice variant CD44v6 for adenoma imaging