Imaging nonequilibrium atomic vibrations with x-ray diffuse scattering

For over a century, x-ray scattering has been the most powerful tool for determining the equilibrium structure of crystalline materials. Deviations from perfect periodicity, for example due to thermal motion of the atoms, reduces the intensity of the Bragg peaks as well as produces structure in the diffuse scattering background. Analysis of the thermal diffuse scattering (TDS) had been used to determine interatomic force constants and phonon dispersion in relatively simple cases before inelastic neutron scattering became the preferred technique to study lattice dynamics. With the advent of intense synchrotron x-ray sources, there was a renewed interest in TDS for measuring phonon dispersion. The relatively short x-ray pulses emanating from these sources also enables the measurement of phonon dynamics in the time domain. Prior experiments on nonequilibrium phonons were either limited by time-resolution and/or to relatively long wavelength excitations. Here we present the first images of nonequilibrium phonons throughout the Brillouin zone in photoexcited III-V semiconductors, indium-phosphide and indium-antimonide, using picosecond time-resolved diffuse scattering. In each case, we find that the lattice remain out of equilibrium for several hundred picoseconds up to nanoseconds after laser excitation. The non-equilibrium population is dominated by transverse acoustic phonons which in InP are directed along high-symmetry directions. The results have wide implications for the detailed study of electron-phonon and phonon-phonon coupling in solids.Comment: 10 pages, 3 figure

Time- and momentum-resolved probe of heat transport in photo-excited bismuth

We use time- and momentum-resolved x-ray scattering to study thermalization in a photo-excited thin single crystal bismuth film on sapphire. The time-resolved changes of the diffuse scattering show primarily a quasi-thermal phonon distribution that is established in less than or similar to 100 ps and that follows the time-scale of thermal transport. Ultrafast melting measurements under high laser excitation show that epitaxial regrowth of the liquid phase occurs on the time-scale of thermal transport across the bismuth-sapphire interface. (C) 2013 AIP Publishing LLC. (DOI: 10.1063/1.4804291

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells

Machine-learning-aided prediction of brain metastases development in non-small-cell lung cancers

Purpose Non–small-cell lung cancer (NSCLC) shows a high incidence of brain metastases (BM). Early detection is crucial to improve clinical prospects. We trained and validated classifier models to identify patients with a high risk of developing BM, as they could potentially benefit from surveillance brain MRI. Methods Consecutive patients with an initial diagnosis of NSCLC from January 2011 to April 2019 and an in-house chest-CT scan (staging) were retrospectively recruited at a German lung cancer center. Brain imaging was performed at initial diagnosis and in case of neurological symptoms (follow-up). Subjects lost to follow-up or still alive without BM at the data cut-off point (12/2020) were excluded. Covariates included clinical and/or 3D-radiomics-features of the primary tumor from staging chest-CT. Four machine learning models for prediction (80/20 training) were compared. Gini Importance and SHAP were used as measures of importance; sensitivity, specificity, area under the precision-recall curve, and Matthew's Correlation Coefficient as evaluation metrics. Results Three hundred and ninety-five patients compromised the clinical cohort. Predictive models based on clinical features offered the best performance (tuned to maximize recall: sensitivity∼70%, specificity∼60%). Radiomics features failed to provide sufficient information, likely due to the heterogeneity of imaging data. Adenocarcinoma histology, lymph node invasion, and histological tumor grade were positively correlated with the prediction of BM, age, and squamous cell carcinoma histology were negatively correlated. A subgroup discovery analysis identified 2 candidate patient subpopulations appearing to present a higher risk of BM (female patients + adenocarcinoma histology, adenocarcinoma patients + no other distant metastases). Conclusion Analysis of the importance of input features suggests that the models are learning the relevant relationships between clinical features/development of BM. A higher number of samples is to be prioritized to improve performance. Employed prospectively at initial diagnosis, such models can help select high-risk subgroups for surveillance brain MRI

Non-gaussian statistics and the relativistic nuclear equation of state

We investigate possible effects of quantum power-law statistical mechanics on the relativistic nuclear equation of state in the context of the Walecka quantum hadrodynamics theory. By considering the Kaniadakis non-Gaussian statistics, characterized by the index $\kappa$ (Boltzmann-Gibbs entropy is recovered in the limit $\kappa\to 0$), we show that the scalar and vector meson fields become more intense due to the non-Gaussian statistical effects ($\kappa \neq 0$). From an analytical treatment, an upper bound on $\kappa$ ($\kappa < 1/4$) is found. We also show that as the parameter $\kappa$ increases the nucleon effective mass diminishes and the equation of state becomes stiffer. A possible connection between phase transitions in nuclear matter and the $\kappa$-parameter is largely discussed.Comment: 8 pages, 8 fifures, LaTe

Discrepancy between German S3 Guideline Recommendations and Daily Urologic Practice in the Management of Nonmuscle Invasive Bladder Cancer: Results of a Binational Survey

Introduction: Guideline recommendations are meant to help minimize morbidity and to improve the care of nonmuscle invasive bladder cancer (NMIBC) patients but studies have suggested an underuse of guideline-recommended care. The aim of this study was to evaluate the level of adherence of German and Austrian urologists to German guideline recommendations. Methods: A survey of 27 items evaluating diagnostic and therapeutic recommendations (15 cases of strong consensus and 6 cases of consensus) for NMIBC was administered among 14 urologic training courses. Survey construction and realization followed the checklist for reporting results of internet e-surveys and was approved by an internal review board. Results: Between January 2018 and June 2019, a total of 307 urologists responded to the questionnaire, with a mean response rate of 71%. The data showed a weak role of urine cytology (54%) for initial diagnostics although it is strongly recommended by the guideline. The most frequently used supporting diagnostic tool during transurethral resection of the bladder was hexaminolevulinate (95%). Contrary to the guideline recommendation, 38% of the participants performed a second resection in the case of pTa low-grade NMIBC. Correct monitoring of Bacille Calmette-Guerin (BCG) response with cystoscopy and cytology was performed by only 34% of the urologists. Conclusions: We found a discrepancy between certain guideline recommendations and daily routine practice concerning the use of urine cytology for initial diagnostics, instillation therapy with a low monitoring rate of BCG response, and follow-up care with unnecessary second resection after pTa low-grade NMIBC in particular. Our survey showed a moderate overall adherence rate of 73%. These results demonstrate the need for sharpening awareness of German guideline recommendations by promoting more intense education of urologists to optimize NMIBC care thus decreasing morbidity and mortality rates

Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients

Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-na&iuml;ve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003&ndash;2.065, p = 0.048; HR: 2.269, 95%CI: 1.053&ndash;4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making