As the online world becomes increasingly democratized and socialized, IT departments, like the mythological three-headed dog Kerberos at the gates of Hades, often stand between communication pros and ...the ability to use new media applications to their advantage. To be fair, your IT colleagues are charged with the massive responsibility of keeping an expensive, complex and continuously obsolescing system up and running 24/7. Communication pros no longer control communication, if they ever really did. Technology is blurring the lines that separate them from their IT colleagues. At the same time, IT no longer controls technology. So walk down the hall and grab a cup of coffee with your IT counterparts. The sooner communication pros start treating IT people as valued communication colleagues, the sooner that three-headed dog will disappear.
Abstract
New three-dimensional (3D) topological phases can emerge in superlattices containing constituents of known two-dimensional topologies. Here we demonstrate that stoichiometric Bi
1
Te
1
, ...which is a natural superlattice of alternating two Bi
2
Te
3
quintuple layers and one Bi bilayer, is a dual 3D topological insulator where a weak topological insulator phase and topological crystalline insulator phase appear simultaneously. By density functional theory, we find "Equation missing"
indices (0;001) and a non-zero mirror Chern number. We have synthesized Bi
1
Te
1
by molecular beam epitaxy and found evidence for its topological crystalline and weak topological character by spin- and angle-resolved photoemission spectroscopy. The dual topology opens the possibility to gap the differently protected metallic surface states on different surfaces independently by breaking the respective symmetries, for example, by magnetic field on one surface and by strain on another surface.
Amyotrophic lateral sclerosis (ALS) is a devastating, adult-onset neurodegenerative disorder of the upper and lower motor systems. It leads to paresis, muscle wasting and inevitably to death, ...typically within 3-5 years. However, disease onset and survival vary considerably ranging in extreme cases from a few months to several decades. The genetic and environmental factors underlying this variability are of great interest as potential therapeutic targets. In ALS, men are affected more often and have an earlier age of onset than women. This gender difference is recapitulated in transgenic rodent models, but no underlying mechanism has been elucidated. Here we report that SNPs in the brain-specific promoter region of the transcriptional co-activator PGC-1 alpha , a master regulator of metabolism, modulate age of onset and survival in two large and independent ALS populations and this occurs in a strictly male-specific manner. In complementary animal studies, we show that deficiency of full-length (FL) Pgc-1 alpha leads to a significantly earlier age of onset and a borderline shortened survival in male, but not in female ALS-transgenic mice. In the animal model, FL Pgc-1 alpha -loss is associated with reduced mRNA levels of the trophic factor Vegf-A in males, but not in females. In summary, we indentify PGC-1 alpha as a novel and clinically relevant disease modifier of human and experimental ALS and report a sex-dependent effect of PGC-1 alpha in this neurodegenerative disorder.
Three-dimensional topological insulators host surface states with linear dispersion, which manifest as a Dirac cone. Nanoscale transport measurements provide direct access to the transport properties ...of the Dirac cone in real space and allow the detailed investigation of charge carrier scattering. Here we use scanning tunnelling potentiometry to analyse the resistance of different kinds of defects at the surface of a (Bi
Sb
)
Te
topological insulator thin film. We find the largest localized voltage drop to be located at domain boundaries in the topological insulator film, with a resistivity about four times higher than that of a step edge. Furthermore, we resolve resistivity dipoles located around nanoscale voids in the sample surface. The influence of such defects on the resistance of the topological surface state is analysed by means of a resistor network model. The effect resulting from the voids is found to be small compared with the other defects.
Focal 68Ga-DOTATATE PET lesions within the myocardium of neuroendocrine tumor (NET) patients are observed in clinical practice. We determined the frequency and characteristics of lesions that are ...consistent with cardiac metastasis and assessed the lesion detection rate of conventional imaging.
629 patients who underwent 68Ga-DOTATATE PET-CT at a supraregional comprehensive cancer center on NET were included from a consecutive registry. Inclusion criteria were: (1) focal 68Ga-DOTATATE tracer uptake within the myocardium in more than two sequential PET exams, and (2) contrast-enhanced CT. To determine the diagnostic accuracy of conventional CT imaging, a case-control cohort with a ratio of 1:3 was used. PET and CT were independently analyzed by two blinded readers. Cohen's κ was assessed for interreader agreement. Descriptive statistics were applied for frequencies and characteristics and group comparisons were analyzed using the Fisher's exact test.
The prevalence of myocardial metastases related to the registry was 2.4% (15 of 629 NET patients fulfilling the inclusion criteria), for a total of 21 myocardial 68Ga-DOTATATE foci detected. Myocardial lesions were most frequently located in the left ventricle (43%) and the septum (43%). No patient demonstrated a pericardial effusion. Patients with myocardial metastases did not differ in demographics, tumor grading, disease stage or circulating tumor markers compared to the overall registry (all p > 0.05). Higher Ki67-Indices were observed (p = 0.049) for patients with myocardial metastases. Interreader agreement for PET assessment was excellent (Cohen's κ = 1.0). CT reading showed a sensitivity of 19% (95% confidence interval: 6-43%) at a specificity of 100% (95% confidence interval: 90-100%).
68Ga-DOTATATE PET enables detection of myocardial metastatic lesions in NET patients. In contrast, standard morphologic CT imaging provides very limited sensitivity.
The aim of this retrospective study was to compare the diagnostic accuracy of somatostatin receptor (SSR)-PET/CT to liver MRI as reference standard in the evaluation of hepatic involvement in ...neuroendocrine tumors (NET).
An institutional database was screened for "SSR" imaging studies between 2006 and 2021. 1000 NET Patients (grade 1/2) with 2383 SSR-PET/CT studies and matching liver MRI in an interval of +3 months were identified. Medical reports of SSR-PET/CT and MRI were retrospectively evaluated regarding hepatic involvement and either confirmed by both or observed in MRI but not in SSR-PET/CT (false-negative) or in SSR-PET but not in MRI (false-positive).
Metastatic hepatic involvement was reported in 1650 (69.2%) of the total 2383 SSR-PET/CT imaging studies, whereas MRI detected hepatic involvement in 1685 (70.7%) cases. There were 51 (2.1%) false-negative and 16 (0.7%) false-positive cases. In case of discrepant reports, MRI and PET/CT were reviewed side by side for consensus reading. SSR-PET/CT demonstrated a sensitivity of 97.0% (95%CI: 96.0%, 97.7%), a specificity of 97.7% (95%CI: 96.3%, 98.7%), a PPV of 99.0% (95%CI: 98.4%, 99.4%) and NPV of 93.0% (95%CI: 91.0, 94.8%) in identifying hepatic involvement. The most frequent reason for false-negative results was the small size of lesions with the majority < 0.6 cm.
This study confirms the high diagnostic accuracy of SSR-PET/CT in the detection of hepatic involvement in NET patients based on a patient-based analysis of metastatic hepatic involvement with a high sensitivity and specificity using liver MRI imaging as reference standard. However, one should be aware of possible pitfalls when a single imaging method is used in evaluating neuroendocrine liver metastases in patients.
\gls{HARQ} schemes are employed in mobile communication systems to reduce the residual Frame Error Rate (FER) after channel decoding. If decoding fails, the receiver requests the transmission of ...additional redundancy about these frames to improve the decoding success. Signaling is carried out over a feedback link from the receiver back to the transmitter. However, errors on the feedback link severely influence the behavior of the HARQ system and may degrade the overall system performance. In this contribution, the impact of HARQ signaling errors on the FER, the average number of HARQ transmissions per frame, and the system throughput is investigated. We derive analytical expressions for all performance measures based on FER simulations of the HARQ system with reliable feedback. The theoretical results are verified by the example of the LTE physical layer, however, they are also applicable to other communication systems. Moreover, target requirements for the maximum tolerable feedback error probabilities are derived which are used to develop design guidelines for HARQ feedback transceivers.
Drug repurposing is used to propose new therapeutic perspectives. Here, we introduce “Drug Upgrade”, that is, characterizing the mode of action of an old drug to generate new chemical entities and ...new therapeutics. We proposed a novel methodology covering target identification to pharmacology validation. As an old drug, we chose hydroxychloroquine (HCQ) for its well‐documented clinical efficacy in lupus and its side effect, retinal toxicity. Using the Nematic Protein Organization Technique (NPOT®) followed by liquid chromatography‐tandem mass spectrometry analyses, we identified myeloperoxidase (MPO) and alpha‐crystallin β chain (CRYAB) as primary and secondary targets to HCQ from lupus patients' peripheral blood mononuclear cells (PBMCs) and isolated human retinas. Surface plasmon resonance (SPR) and enzymatic assays confirmed the interaction of HCQ with MPO and CRYAB. We synthesized INS‐072 a novel analog of HCQ that increased affinity for MPO and decreased binding to CRYAB compared to HCQ. INS‐072 delayed cutaneous eruption significantly compared to HCQ in the murine MRL/lpr model of spontaneous lupus and prevents immune complex vasculitis in mice. In addition, long‐term HCQ treatment caused retinal toxicity in mice, unlike INS‐072. Our study illustrates a method of drug development, where new applications or improvements can be explored by fully characterizing the drug's mode of action.
The complex mechanics of the gastric wall facilitates the main digestive tasks of the stomach. However, the interplay between the mechanical properties of the stomach, its microstructure, and its ...vital functions is not yet fully understood. Importantly, the pig animal model is widely used in biomedical research for preliminary or ethically prohibited studies of the human digestion system. Therefore, this study aims to thoroughly characterize the mechanical behavior and microstructure of the porcine stomach. For this purpose, multiple quasi-static mechanical tests were carried out with three different loading modes, i.e., planar biaxial extension, radial compression, and simple shear. Stress-relaxation tests complemented the quasi-static experiments to evaluate the deformation and strain-dependent viscoelastic properties. Each experiment was conducted on specimens of the complete stomach wall and two separate layers, mucosa and muscularis, from each of the three gastric regions, i.e., fundus, body, and antrum. The significant preconditioning effects and the considerable regional and layer-specific differences in the tissue response were analyzed. Furthermore, the mechanical experiments were complemented with histology to examine the influence of the microstructural composition on the macrostructural mechanical response and vice versa. Importantly, the shear tests showed lower stresses in the complete wall compared to the single layers which the loose network of submucosal collagen might explain. Also, the stratum arrangement of the muscularis might explain mechanical anisotropy during tensile tests. This study shows that gastric tissue is characterized by a highly heterogeneous microstructure with regional variations in layer composition reflecting not only functional differences but also diverse mechanical behavior. STATEMENT OF SIGNIFICANCE: Unfortunately, only few experimental data on gastric tissue are available for an adequate material parameter and model estimation. The present study therefore combines layer- and region-specific stomach wall mechanics obtained under multiple loading conditions with histological insights into the heterogeneous microstructure. On the one hand, the extensive data sets of this study expand our understanding of the interplay between gastric mechanics, motility and functionality, which could help to identify and treat associated pathologies. On the other hand, such data sets are of high relevance for the constitutive modeling of stomach tissue, and its application in the field of medical engineering, e.g., in the development of surgical staplers and the improvement of bariatric surgical interventions.
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