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Investigation of Inertial Cavitation of Sonosensitive and Biocompatible Nanoparticles in Flow - Through Tissue- Mimicking Phantoms Employing Focused Ultrasound
No full textA promising approach to drug delivery applications for chemotherapeutics is the use of drug carriers to reduce the total amount of cytostatics, minimizing side effects. In addition, the carriers, loaded with the drug, can be guided to the tumorous tissue via the vascular system, which enables a local drug release (LDR). In our case, LDR is activated due to the sonosensitive behavior of the nanocapsules by inertial cavitation (IC) caused by focused ultrasound (FUS). Thereby, IC is excited by employing sound pressures within the recommended limit allowed for diagnostic ultrasound. In order to verify this drug delivery approach for its clinical suitability, a tissue-mimicking flow -through phantom, containing a small vessel, is used. Investigations have shown that the drug releasing cavitation effect associated with the sonosensitive and biocompatible nanocapsules also occurs in fine vessel structures, even in the case of moving particles and vessel diameters dc smaller than the wavelength λ
Explaining and Evaluating Deep Tissue Classification by Visualizing Activations of Most Relevant Intermediate Layers
No full textDeep Learning-based tissue classification may support pathologists in analyzing digitized whole slide images. However, in such critical tasks, only approaches that can be validated by medical experts in advance to deployment, are suitable. We present an approach that contributes to making automated tissue classification more transparent. We step beyond broadly used visualizations for last layers of a convolutional neural network by identifying most relevant intermediate layers applying Grad-CAM. A visual evaluation by a pathologist shows that these layers assign relevance, where important morphological structures are present in case of correct class decisions. We introduce a tool that can be easily used by medical experts for such validation purposes for any convolutional neural network and any layer. Visual explanations for intermediate layers provide insights into a neural network’s decision for histopathological tissue classification. In future research also the context of the input data must be considered
“Time without you”: Transition to widowhood and its impact on time perspective and attitudes toward the future
No full textWidowhood is a significant life event that can profoundly alter an individual’s perception of time. Those who have lost a spouse often find themselves reflecting on past memories, while simultaneously feeling disconnected from the present. However, the impact of widowhood on one’s experience and perception of time has not been thoroughly explored. In this study, we investigate changes in time perspective during the transition to widowhood using a multidimensional approach to temporal experience. This perspective enriches the existing literature, which has primarily focused on the predictive role of time perspective by providing new insights into how major life events can reshape an individual’s experience of time. The sample was drawn from seven measurement points between 2009 and 2023 in the Aging-as-Future longitudinal study. It consisted of 1357 participants aged 50 and older who either remained married throughout the study period ( n = 1270) or transitioned to widowhood ( n = 87). We assessed four facets of time perspective: past-orientation, feelings of obsolescence, concreteness of the future time, and attitudes toward life’s finitude as well as subjective life expectancy. While the transition to widowhood predicted an increase in past-orientation and in feelings of obsolescence, it predicted a decrease in concreteness of the future. Spousal loss did not influence individuals’ attitudes toward finitude, but those experiencing widowhood reported a decrease in their perceived remaining lifetime. Our study showed that widowhood may lead to shifts in time perspective. Findings underscore the value of considering time perspective as a key indicator of an individual’s adjustment and functioning in response to a major life event.Open Access funding enabled and organized by Projekt DEAL.Volkswagen Foundationhttp://dx.doi.org/10.13039/501100001663Friedrich-Schiller-Universität Jena (1010
More hyperelastic models for rubber-like materials: consistent tangent operators and comparative study
No full textRubber-like materials can deform largely and nonlinearly upon loading, and they return to the initial configuration when the load is removed. Such rubber elasticity is achieved due to very flexible long-chain molecules and a three-dimensional network structure that is formed via cross-linking or entanglements between molecules. Over the years, to model the mechanical behavior of such randomly oriented microstructures, several phenomenological and micromechanically motivated network models for nearly incompressible hyperelastic polymeric materials have been proposed in the literature. To implement these models for polymeric material (undoubtedly with widespread engineering applications) in the finite element framework for solving a boundary value problem, one would require two important ingredients, i.e., the stress tensor and the consistent fourth-order tangent operator, where the latter is the result of linearization of the former. In our previous work, 14 such material models are reviewed by deriving the accurate stress tensors and tangent operators from a group of phenomenological and micromechanical models at large deformations. The current contribution will supplement some further important models that were not included in the previous work. For comparison of all selected models in reproducing the well-known Treloar data, the analytical expressions for the three homogeneous defomation modes, i.e., uniaxial tension, equibiaxial tension, and pure shear, have been derived and the performances of the models are analyzed
Enhanced bioactivity and degradation behavior of zinc via micro-arc anodization for biomedical applications
No full textZinc-based alloys have attracted increasing interest as absorbable implant metals due to their suitable degradation rate and biocompatibility. However, a high concentration of Zn 2+ due to the degradation process results in high cytotoxicity, and low osteogenesis remains a problem. In this work, a compact coating well integrated into the substrate was fabricated on the surface of zinc via micro-arc oxidation (MAO). The coating is mainly composed of ZnO. The addition of phosphate in the coating reinforced the adhesive strength between Zn and the coating. Electrochemical measurements demonstrate a superior corrosion resistance of MAO-P samples as compared to the substrate. Long-term immersion measurements in simulated body fluid indicate that the coating improved the bioactivity of the substrate, which is promising in view of orthopedic applications
O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE
No full textFor successful colonization, pathogenic bacteria need to adapt their metabolism and virulence functions to challenging environments within their mammalian hosts that are frequently characterized by low oxygen (O2) tensions. Upon oral ingestion, the human pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) is exposed to changing O2 and pH levels. Low concentrations of O2, which can enhance the virulence of enteroinvasive pathogens, facilitate the expression of the type three secretion system (T3SS-1) encoded by the Salmonella pathogenicity island 1 (SPI-1) that is critical for enteroinvasion and pathogenicity of S. Typhimurium. To study the impact of key environmental cues of the intestine when Salmonella encounter enterocytes, we established an in vitro growth model, which allows shifting the concentration of O2 from 0.5% to 11% and the pH from 5.9 to 7.4 in the presence of acetate and the alternative electron acceptor nitrate. Compared to normoxia, hypoxia elevated the expression of SPI-1 genes encoding T3SS-1 translocators and effectors, which resulted in higher invasion and effector translocation in epithelial cells. While hypoxia and pH shift only marginally altered the gene expression of SPI-1 regulators, including the SPI-1 repressor hilE, hypoxia and pH shift completely incapacitated HilE in a post-translational manner, ultimately promoting SPI-1 activity. From these findings, we conclude that O2-dependent HilE function allows for ultrasensitive adaptation of SPI-1 activity in environments with varying O2 availability such as the intestinal tract
Umwandlung eines organischen Moleküls in ein effizientes optomechanisches System
Get PDFMolecules lie at the heart of chemical and biological processes, and are regarded as building
blocks of organic matter. Their small size, rich and controllable quantum mechanical
properties such as the electronic, vibrational and spin degrees of freedom also make them
ideal candidates for building blocks of future quantum technologies. However, the quantum
coherence of their vibrational states is lost within picoseconds due to coupling to the solidstate
environment. While organic molecules act as effective two-level optical emitters, the
lack of further coherent transitions limits their promise for certain quantum technologies. In
this thesis, we theoretically investigate the nature of the coupling between the electronic and
mechanical degrees of freedom of a molecule embedded in a solid. Based on these insights,
we propose a new molecular platformto revive the optomechanical character and multi-level
structure of an organic molecule in the solid state.
We investigate the vibrational landscape of organic molecular systems and model the photophysics
of a single molecule in solid state from first principle considerations. Using the polaron
master equations and quantum Langevin formalism, we derive analytical formulas for
the excitation and emission spectra at the weak laser excitation limit, and study the optomechanical
interactions. Our results retrieve the well-known Franck-Condon and Debye-Waller
physics. We discuss the relevance of various phonon modes to the the optical dephasing process.
In addition, the importance of anharmonic interactions in the vibrational relaxation
mechanism is demonstrated.
Using finite element simulations, we study the effect of the substrate, crystal size and
shape on the phonon lifetimes. We ultimately engineer the phononic environment of a
molecule, and achieve molecular coherence times beyond the millisecond timescale. To
predict the electron-phonon coupling strengths, we develop the quasi-normal mode theory
for phononic environments. Our results demonstrate that the proposed molecular platformcould
achieve high electron-phonon coupling strengths compared to the electronic and
phonon decoherence rates. These enhanced optomechanical qualities of a molecule ensure
optically accessible long-lived molecular states.
We highlight the optomechanical character of the proposed molecular platformfurther by
studying its spectroscopic signatures. The excitation spectrum shows well-defined phononic
transitions and breakage of Kasha’s rule. Moreover, the resonance fluorescence spectrum reveals
anti-Stokes Raman scattering features at zero phonon bath temperature, and evidences
the high optomechanical cooperativity at the single-photon level. These high-cooperativity
interactions in the proposed molecular platform further allows us to demonstrate a low
threshold molecular phonon laser.
Exploiting the improved optomechanical qualities in the molecular platform, we demonstrate
a single-molecule quantum memory for a single-photon pulse. The memory dynamics
is modelled with analytical formulas based on the quantum Langevin equations. We characterize
the storage and retrieval efficiencies by using the input-output formalism. The analytical
results reveal the universal memory constant uniquely determining the memory efficiencies.
Moreover, we perform a parametric study and pulse optimization to explore the limits
of the memory efficiencies.
Our proposal provides ways of restoring the multi-level character of a molecule, and render
organic molecules high-performance quantum optomechanical systems. The molecular
quantum memory proposed in this thesis opens up prospects for realizing quantum networks
via photonic and phononic interconnections.Moleküle sind dieBausteine organischerMaterie und spielen eine zentraleRolle in chemischen
sowie biologischen Prozessen. Durch ihre nanoskopischen Dimensionen und die vielfältigen
quantenmechanischen Freiheitsgrade, wie zum Beispiel elektronische, Vibrationssowie
Spin-Zustände, sind Moleküle attraktive Systeme zukünftiger Quanten-Technologien.
Während organische Moleküle wegen ihres elektronischen Übergangs effektiv als Zwei-
Niveau-Systeme betrachtetwerden können, fehlen ihnen jedochweitere kohärente Übergänge,
die essentiell für bestimmte Quantenprotokolle sind. Vor allem die Kohärenz der potentiell
interessanten Vibrationszustände geht wegen mechanischer Kopplung an die Festkörperumgebung
innerhalb von Pikosekunden verloren. In dieser Arbeit wird die Kopplung elektronischer
und mechanischer Freiheitsgrade eines Moleküls und seiner Umgebung theoretisch
untersucht. Wir nutzen die daraus gewonnen Erkenntnisse um eine neue Plattform vorzuschlagen,
in welcher der optomechanische Charakter einesMoleküls erhalten bleibt, so dass
mehr als nur zwei Zustände einesMoleküls genutzt werden können.
Wir nutzen einen fundamental quantenmechanischen Ansatz, um die Photophysik und
die Vibrationseigenschaften organischer Molekülkristalle zu beschreiben. Mithilfe der Polaron
Master Gleichung und eines Quanten-Langevin Ansatzes, leiten wir analytische Ausdrücke
für die Anregungs- sowie Emissionsspektren im Regime niedriger Anregungsleistungen
her und charakterisieren die optomechanischen Wechselwirkungen. Als Resultat ergeben
sich die bekannte Franck-Condon sowie Debye-Waller Physik. Zudem diskutieren wir
anhand dieses Ansatzes, wie individuelle Phonon-Moden zur Dephasierung des optischen
Übergangs beitragen. Zusätzlich lässt sich aus diesen Betrachtungen die Relevanz anharmonischer
Kopplung für die Vibrations-Relaxation erkennen.
Mithilfe von Finite-Elemente-Simulationen charakterisieren wir den Zusammenhang
zwischen den Lebenszeiten von Phononen in molekularen Kristallen mit deren Größe und
Form sowie den Eigenschaften des Substrats. Basierend auf diesen Ergebnissen modifizieren
wir die phonische Umgebung eines Moleküls derart, dass die Lebenszeiten phononischer
Zustände dieMillisekunden-Marke überschreiten.Umdie Stärke der Elektron-Phonon-
Kopplung zu beschreiben, entwickeln wir eine entsprechendeQuasi-Normalmoden-Theorie.
Dieser Ansatz zeigt, dass die Elektron-Phonon-Kopplung in dem von uns vorgeschlagenem
System stärker als die elektronischen und phononischen Dekohärenzraten werden kann.
Durch die Verstärkung der optomechanischen Wechselwirkungen in diesem System können
langlebige Zustände desMoleküls somit effektiv adressiert werden.
Wir beschreiben den optomechanischen Charakter der vorgeschlagenen Plattformaußerdem
anhand spektroskopischer Merkmale. Im Anregungsspektrum lassen sich wohldefinierte
phononische Übergänge sowie eine Verletzung der Kasha-Regel erkennen. Das Fluoreszenz-Spektrum enthält Anti-Stokes Linien während das Phonon Reservoir eine Temperatur
von 0 K hat, eine Folge der hohen optomechanischen Kooperativität der vorgeschlagenen
molekularen Plattform auf Einzel-Photonen-Niveau. Diese hohe Kooperativität führt
außerdem dazu, dass ein molekularer Phonon-Laser mit niedriger Schwelle möglich ist.
Ein langlebiger Zustand sowie die starke optomechanischeWechselwirkung ermöglichen
es, einzelne Photonen kohärent in einem Molekül zu speichern. Wir analysieren ein mögliches
Speicher-Protokoll mithilfe analytischer Formeln, die ausgehend von einem Quanten-
Langevin-Ansatz hergeleitet werden können. Die Speicher- und Auslese-Effizienzen berechnen
wir dabei im Input-Output Formalismus. Die analytischen Ergebnisse werden dazu genutzt,
eine universellen Speicher-Konstante zu bestimmen, die die Speicher-Effizienz eindeutig
charakterisiert. Darüber hinaus führen wir eine Parameter-Studie und eine Puls-
Optimierung durch, um die Grenzen der Speicher-Effizienz zu auszuloten.
Unser Vorschlag für eine Plattform mit langlebigen molekularen Zuständen zeigt, wie
mehr als nur zwei Niveaus eines Moleküls effektiv genutzt werden können und wie ein Molekül
somit als leistungsstarkes optomechanisches System agieren kann. Dieser molekulare
Speicher könnte zukünftig für Quantennetzwerke mit photonischen und phononischen Kanälen
genutzt werden
Implementing complete mesocolic excision for colon cancer – mission completed?
No full textThe definition of complete mesocolic excision (CME) for colon carcinomas revolutionized the way of colon surgery. This technique conquered the world starting from Erlangen. Nevertheless, currently new developments especially in minimally invasive surgery challenge CME to become settled as a standard of care. To understand the evolution of CME, anatomical details occurring during embryogenesis and their variations have to be considered. This knowledge is indispensable to transfer CME from an open to a minimally invasive setting. Conventional surgery for colon cancer (non-CME) has a morbidity of 12.1–28.5% and a 3.7% mortality risk vs. 12–36.4% morbidity and 2.1–3% mortality for open CME. The morbidity of laparoscopic CME is between 4 and 31% with a mortality of 0.5–0.9%. In robotic assisted surgery, morbidity between 10 and 25% with a mortality of 1% was published. The cancer-related survival after 3 and 5 years for open CME is respectively 91.3–95% and 90% vs. 87% and 74% for non-CME. For laparoscopic CME the 3- and 5-year cancer-related survival is 87.8–97% and 79.5–80.2%. In stage UICC III the 3- and 5-year cancer-related survival is 83.9% and 80.8% in the Erlangen data of open technique vs. 75.4% and 65.5–71.7% for laparoscopic surgery. For stage UICC III the 3- and 5-year local tumor recurrence is 3.8%. The published data and the results from Erlangen demonstrate that CME is safe in experienced hands with no increased morbidity. It offers an obvious survival benefit for the patients which can be achieved solely by surgery. Teaching programs are needed for minimally invasive CME to facilitate this technique in the same quality compared to open surgery. Passing these challenges CME will become the standard of care for patients with colon carcinomas offering all benefits of minimally invasive surgery and oncological outcome